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Russian Academy of Medical Sciences, Medical-Biological Department

P.K.Anokhin Institute of Normal Physiology RAMS


I.M.Sechenov First Moscow Medical University
International Academy of Science (Health & Ecology)
Russian Physiological Society (Moscow Branch)
Russian Neurochemical Society
RAMS Scientific Council of Experimental and Applied Physiology

3d International Interdisciplinary Conference on

MODERN PROBLEMS IN SYSTEMIC REGULATION OF


PHYSIOLOGICAL FUNCTIONS

ABSTRACTS

Limassol, Cyprus, October 1-8, 2013




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INFORMATIONAL BRAIN SYSTEM QUANTA OF ACCEPTORS OF ACTION


RESULTS IN DYNAMICS OF SYSTEM ORGANIZATION OF PSYCHIC
ACTIVITY AND BEHAVIOR
Sudakov K.V.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
Department of normal Physiology, I.M. Sechenov First Moscow State
Medical University, Moscow, Russia
ksudakov@mail.ru
Nowadays
in
natural
sciences
interest
to
informational
organization of psychic activity of humans and animals has considerably
grown.
Information processes become apparent in activity of organism
functional systems discovered by P.K. Anokhin.
In functional systems formed on morpho-functional structures of
organism the information about the state useful for the organism
results regulated by them in the form of informational equivalents,
postulated by Anokhin is constantly circulating.
The leading role in valuation of information in system
architectonics of psychic activity and behavior belongs to a stage of
acceptor of action results, which is formed by previous stages of
afferent synthesis and decision-making and becomes enriched by
evaluation and fixation of the achieved by subjects behavioral results
by means of reverse afferentation.
Acceptors of action results in every functional system present a
multi-level cerebral organization that unites dominant motivational
8

excitation, pyramidal
cortex neurons, pyramidal tracts and multiple
interneurons of cortex and subcortical structures on which efferent
excitations
of pyramidal neurons and reverse afferentation from
parameters achieved by subjects results in dynamics of their behavioral
activity are distributed by collaterals of pyramidal tracts.
Dynamics of activity of organism functional systems is built by
discreet system quanta: from needs to their satisfaction.
Just on the structures of acceptors of action results interaction
of informational equivalents of motivational excitations are realized.
As a result of interaction of motivational and reinforcing excitations
on morpho-functional organization of acceptors of action results
different dynamically changed geometrical images are formed which we
consider as informational equivalents which externally show themselves
as autonomic and behavioral system quanta. Hypothetically we think that
these informational images are dynamically changing holograms formed
under interferention of two waves: signalization about need and
signalization about its satisfaction.
On morpho-functional organization of acceptor of action results of
different functional systems under interaction of informational
equivalents of needs and their satisfaction informational system quanta
are formed.
We think that informational equivalents of cerebral processes of
interaction of motivation and reinforcement on morpho-functional
organization of acceptor of action results constitute an ideal side of
reflection by brain originated in it material physiological processes.
Meanwhile in functional systems material physiological and ideal
informational processes present inseparable unity.
In construction of system quanta information synergetic properties
are apparent. Molecular matrixes of acceptors of action results present
peculiar tree the branches of which are changed when informational
equivalents of needs and parameters of their satisfaction
come to
them. Newly formed images are imprinted by memory mechanisms. In the
process of learning of live subjects on the base of memory mechanisms
continuously take place enrichment, fixation or, on the contrary,
reduction of informational system quanta of acceptors of action results
that is their molecular tree.
Interaction of informational system quanta on the structures of
acceptors of action results is realized on the principles of dominant
hierarchy, multiparametrical and sequential interaction and principle
of systemogenesis.
Under alternate formations of needs either dominant motivations or
environmental and special conditioned stimuli in advance retrieve
accumulated by previous subjects experience informational systemquants
of acceptors of action results. All these processes are continuously
accompanied by corresponding emotional feelings: negative ones under
formation of need and positive under its satisfaction.
Hypothetically one should think that under influence of signals
from needs and their satisfactions in molecules and atoms which
constitute system quanta of acceptors of action results reorganization
of inner elementary particles: electrons, mesons, quarks etc. takes
place. Meanwhile moments of their impulses-spins, rotator spectrums,
9

absorption spectrum, quantum yield of fluorescence and other processes


are changing. As a result informational molecular and atom images of
needs and in advance images of their possible satisfaction are formed.
It is possible to think that at these moments relocation of
electrons on far orbits accompanied by energy release, luminescent
quant outbursts or weak acoustic signals takes place. Under
satisfaction of needs electrons return on their initial orbits that
forms geometrical images of reinforcement. It is likely that emotional
signals fundamentally influence on intra-atomic processes.
Informational system quanta participate in formation and
manifestation of conciseness processes, accumulation in memory
acceptors of action results of functional systems of experience
(knowledge) accompanied by emotional signals and its retrieval by
dominant motivations, environmental and trigger conditioned stimuli.
Under the influence of inner needs and exogenously under external
environmental or conditioned- reflex factors and as well as special
instructions the thoughts as informational equivalents of reality with
accompanying emotions are formed by informational system quanta.
Informational system quanta of thoughts initially manifest
themselves without outward appearance in the form of interbrain ideal
informational essence.
Formed by brain informational system quanta thoughts outwardly
manifest themselves in the form of material processes: behavior,
gestures, autonomic reactions and in humans by language and different
forms of creative activity. As analogs with technical devices
informational system quanta of acceptors of action results play the
role of decoders, comparators, navigators and vectors of behavioral and
psychic activity of humans and animals.

10

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abdulkerimovas@mail.ru


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THE EFFECT OF CRUDE OIL ON MORPHO-FUNCTIONAL STATUS OF COMMON


CARP LIVER
Abdulkerimova S.L.
A.I.Karaev Institute of Physiology NAS of Azerbaijan, Baku, Azerbaycan
abdulkerimovas@mail.ru
The effects of crude oil from the Azeri deposit on of common
carps (Cyprinus carpio L.) liver tissue in the initial stages of
exposure have been studied. Influence of two concentration of the said
oil was investigated at 100 and 500 ppm. Controls were kept in clean
water. The dynamics of the histological alterations of this tissue 1,
3, 6, 24, 48, 72 and 96 h after exposure was examined. The taken
samples of liver tissue were fixed in neutral buffered 4 % formalin.
After dehydration and embedding in paraffin the cuts of 7 m thickness
have been stained with hematoxylin-eosin (HE). The cuts were analyzed
under the light microscope.
Hepatocytes in the liver tissue of the control group had no
abnormalities, with distinct borders, homogeneous cytoplasm and
centrally located nucleus. In the liver tissue of experimental group,
exposed in the water contaminated with crude oil at a concentration of
100 ppm for first day did not lead to essential alterations.
Vacuolization and some blood stagnation in the vessels up to 48 h of
oil exposure were noticed.
It was revealed the close location of
nuclei to the periphery of the hepatocytes and accumulation of large
amounts of melanomacrophages up to 72 h and 96 h. The impact of crude
oil at a concentration of 500 ppm resulted in a minimal vacuolization
of hepatocytes in 24-hour exposure. At 48- hour exposure the presence
of single melanomacrophage centers and stagnation of blood were
observed. Increased number of melanomacrophage centers, dilatation of
sinusoids, and advent of karioretic and picnotic nuclei in hepatocytes
and necrotic cells up to 72 h and 96 h of exposure were observed.
The data indicate that severity of histological changes in the hepatic
tissue of carp are directly dependent of increasing of exposure time
and concentration of crude oil. It is known that one of the main liver
functions is
detoxication that maintains persistence of the blood
composition of the organism. The changes observed in hepatocytes may
lead to morpho-functional pathological changes of the liver tissue,
which may affect the future life of the fish, because of intoxication
of the organism.
So, the crude oil from the Azeri deposit causes a number of
histological changes of the hepatic tissue of common carp that are
probably related to the direct effects of polyaromatic hydrocarbons
(PAH) on the cellular elements of fish. The data concerning carps
liver tissue sensitivity give grounds to use this type of analysis as
biomarker to assess quality of the environment milieu.

12



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DYNAMICS OF DIFFERENCES IN THE DEVELOPMENT OF SEARCH BEHAVIOR


FOR MOTHER AND SIBLINGS AT EARLY AGE IN WISTAR RATS
Aleksandrova E. A., Zarayskaya I. Yu.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
e_alexandrova2002@yahoo.com
The successful development of social behavior is of particular
importance for the acquisition of individual experience. The objective
of this study was to investigate characteristics of the formation of
functional systems for social search in early ontogeny. Studies
performed earlier at the P.K. Anokhin school were focused mainly on the
relationship between mother (or parents) and offspring (Bogomolova,
1976, 1985; Shulejkina, 1971). Our task was to make a comparative
analysis of the dynamics of development of search for mother or
littermates in altricial laboratory rats in the first half of the nest
period.
The experimental approach to the problem was based on the ability
of altricial rodents for early olfactory discrimination learning.
Olfactory learning of Wistar rats offspring was carried out from 4 to
11 postnatal day (pnd) The first group of pups of different ages, in
accordance with the well known procedure (Sullivan et al., 1991) was
trained in "search for mother" task. Following isolation of the pup
from the mother and littermates for 40 min, the training procedure
consisted of stroking of the body with a soft brush (imitation of
maternal licking) combined with presentation of a new odor in the box
with sawdust moistened with peppermint extract. Three pre-isolated rats
of the second group ("search for siblings") were placed for training in
the same box. Each animal from the group of "control" was placed in the
same box without any treatment. The exposition to the new odor for the
pups of all three groups was 10 minutes. After the training session,
rats were returned to the home cage where they stayed with their mother
and littermates for 24 hours. Then olfactory testing was performed
after 40-minute deprivation from mother and littermates. Each pup was
placed on a plastic perforated platform, divided by a neutral zone (1.5
14

cm without perforation) into two compartments: one with clean sawdust


under the floor and the second (test) with sawdust moistened with
peppermint extract under the floor. For testing, the rat was placed on
the neutral zone. Time spent in each compartment was recorded during
five one-minute trials.
The results of testing. 24 hours after exposure to the new smell,
animals of all studying ages from the control group spent from 17 to
34% of the test time in the test compartment, which means that the
smell of peppermint extract did not cause preference in this group.
Rats that were trained to find the mother at 4-10 days after birth
spent from 48 to 60% of the test time over the test compartment with
peppermint smell, but 11-days animals did not show such odor preference
and their score was 35%, which did not differ from the result of the
control animals. Training in "search for siblings", on the contrary,
was effective only on 9, 10, and 11 pnd, when the time in the test
compartment was 54, 58 and 75% of the test time, respectively. The
preference of the test odor in the group "search for siblings at day
11 exceeded this figure in the group "search for mother".
Thus, in Wistar rats pups the comparison of the dynamics of
learning to find contact with mother or littermates in the first half
of the nest period indicates a shift of social interest in young rats
starting from 9 pnd. This period is characterized by a decreasing
activity of maternal care, which is likely to affect the effectiveness
of training for searching a contact with mother. At the same time,
development of necessary components of the search for a contact with
littermates occurs (Alexandrova et.al. 1997). The results of the study
allow us to recommend the use of two models of early social learning
for the phenotype of offspring rodents.



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16

ENGAGEMENT OF SUBCELLULAR COMPONENT OF SEROTONERGIC SYSTEM IN


LAUNCHING AND SUPPRESSION OF EPILEPTIC SEIZURES
Allahverdiyeva A.M., Panahova E.N., Mekhtiev A.A.
A.I.Karaev Institute of Physiology, NAS of Azerbaijan, Baku, Azerbaycan
arifmekht@yahoo.com
Studies in experimental models in animals and clinical studies have
shown that epileptic seizures are developed on the background of
downregulation of serotonin in the organism. The goal of the study was
analysis of the role of a novel serotonin-modulating anticonsolidation
protein (SMAP; Mekhtiev, 2000), being in linear relationship with
serotonin level and, perhaps, realizing its functions on subcellular
level, in formation and suppression of seizure activity in Shinshilla
rabbits. The experiments were conducted in compliance to the
requirements of main ethic guidelines.
In the 1st series of studies epileptic seizures were induced in
animals through application of 300 units of sodium salt of penicillin
via chemodes implanted prior into the amygdala. The epileptic locus in
amygdala 30-40 min later led to formation of prolonged clonic seizures
in the animals. In this case significant modulations of patterns of the
evoked potentials (EP) to light splashes in the visual cortex (VC),
colliculus superior (CS) and retina as well as interictal spikes were
fixed. Seizures lasted totally for 3 h.
Intramuscular SMAP administration (3.5 ml, 1.5 mg/ml) after 30-40
min led to suppression of clonic seizures in animals. In the said brain
structures elimination of interictal spikes was observed, however
increased excitation of neuronal ensembles maintained a little longer.
Recovery of original parameters of EP after SMAP injection occurred in
inverse order: first in retina, SC, VC and later of all in amygdala. In
a separate experiment it was demonstrated that intramuscular
administration to rabbits of the same SMAP amount led to four-time
increase of its level (ELISA-test) in the liquor indicating to
permeability of HEB for SMAP.
In the 2nd series of studies 2.5-4 h after administration of the
anti-SMAP rabbit polyclonal antibodies (20 g) into the amygdala
development of whole picture of epileptic activity in the form of
clonic seizures and changes of patterns of EP in VC, CS and retina and
advent of interictal spikes all similar to those appeared in the 1st
series of studies after application of penicillin solution to the
amygdala was noticed.
In the 3rd series of studies the rabbits were immunized with SMAP
and after 40 days high titers of anti-SMAP immunoglobulins were
revealed in their blood and EP were fixed in VC, CS and retina and the
values of their indexes prior to and after immunization were compared.
It was found that in the CS amplitude of positive wave decreased 2
times and its duration got shorter, while amplitude of negative wave
sharply increased (3 times) with simultaneous decrease of its duration.
In the VC decrease of the amplitude of positive wave to its complete
disappearance with parallel increase of amplitude (3 times) and
17

duration (3 times) of the positive and negative waves of secondary EPs


and advent of doubled EPs was observed. These animals were applied
through chemodes with 200 units of penicillin which did not induce
seizures in the nave animals. After 40 min development of both
external manifestations and electrographic indexes of epileptic
activity in the VC, CS and retina were noticed in the immunized
animals.
The data indicate to SMAP participation in development of seizure
activity: blocking of SMAP activity with antibodies in the amygdala
induces launching of epileptic activity, whereas its administration to
the animals with formed epileptic seizures leads to suppression of both
their external manifestations and recovery of the electrographic
indexes.



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ANALYSIS OF SELECTION AND CATEGORIZATION OF FRAGMENTED VISUAL


OBJECTS IN HEALTHY HUMANS
Astashchenko A.P., Dorohov E.V., Kashchenko I.S.
Voronezh State Medical Academy named N.N. Burdenko, Voronezh,
Russia
cercea1@rambler.ru.
In ordinary environments, objects are often not clearly perceived
because of poor lighting, shadows, partial occlusion by other objects,
and so forth. In these cases, object becomes fragmented (incomplete)
and object categorization is markedly slower. The visual system of
healthy adult person can rapidly categorize clearly perceived, single
objects into a known class. There are evidences in which was observed
effects of recognition (decision-making) simple images to reflect in
the range 300 500 ms. Selection and categorization of fragmented
visual objects are decision of more complex task, where time was spent
19

on the identification of the object, depends on quantity received the


necessary information. The research object is studying peculiarities of
time decision-making of fragmented images in healthy adult persons.
Twenty- two right-handed 2nd year students of medical academy with
normal vision (10 males and 12 females; mean age=18-20 years),
volunteered to participate in the study. In all cases, was obtained the
ethical consent for the study. We have developed a special method for
registration time object recognition and measurement the thresholds of
perception of incomplete figures on the base of Gollins method for
investigation attention, memory and intelligence in different age
groups. Images were presented in 7 levels of incompleteness (90%, 85%,
80%, 75%, 70%, 65% and 0%). The degrees of incompleteness of the
object's contour were expressed in percentage of fragmentation (percent
of full contour). We analyzed the time of final decision-making about
object and quality (congruence of image interpretation with the
standard). It was detected, that time and quality of selection and
categorization of fragmented images didnt dependent from volunteers
gender. According to many authors, in first presentation of images, the
perception thresholds of incomplete figures are from 4 to 32% (percent
of full contour). In our scientific work 247% was optimal number of
fragments (percent of full contour). Analysis of obtained data allowed
us to share our volunteers on two groups: persons, who makes quick
decisions about visual objects (2095204 ms) and persons, who makes
slow decisions about visual objects (4001248 ms). We assume that a
person's ability to selection and categorization associated with
hemispheric differences in brain activity. It may be to underlie
different strategies of image analysis. We have analyzed data of the
correct decisions about objects and incorrect decisions. This data
allowed us to conclude, that in cases of incorrect decisions about
objects volunteers are spending more time (6191588 ms) comparing with
correct decisions about objects (3003218 ms). It didnt depend on
volunteers group (fast or slow), p=0.0002. From the point of view of
Theory of functional systems, the organization of purposeful behavior
act occurs step by step: formation of acceptor result of the action
(ARA) as a functional apparatus of prognosis and estimation of
execution behavioral program; realization of behavioral program and
their correction and estimation of achieved results. We suppose that
the processes of agreement or disagreement in acceptor result of the
action can influence on time of object selection and define
characteristics of categorization of visual objects in humans.

20


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11.G34.31.0071 21.10.2011.

3D ANALYSIS OF NEUROGENESIS IN THE HIPPOCAMPUS


OF ADULT MICE
Barykina N.V., Shuvaev S.A., Lazutkin A.A., Enikolopov G.N.
Brain Stem Cells Laboratory, NBIC-department, MPTI, Dolgoprudny, Russia
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia Cold
Spring Harbor Laboratory, USA
le.nucleol@gmail.com
The standard protocol of dividing cells identification involves
counting of labeled nuclei in individual sections and the subsequent
extrapolation of the number of cells to the volume of whole
hippocampus. The aim of this work was to develop a methodology for
visualization of stem and proliferating cells in the whole hippocampus
of adult transgenic mice using click-chemistry and immunohistochemistry
(IHC) and to develop a method of neurogenesis quantitative analysis in
3D images. Also the aim of the study was to apply developed technique
for quantify the number of dividing cells in mice exposed to fast
neutron irradiation at dose 0.5 Gy.
The study was conducted on male transgenic mice from the line
NestinCFPnuc (weigh about 30 g); their genome contained a construction
of cyan fluorescent protein (CFP) under nestin promoter. 2 h before
transcardial perfusion mice were injected with 123 mg/kg EdU (5ethynyl-2'-deoxyuridine) ip., which was used as a marker of dividing
cells. Mice were anesthetized with zoletil-xylazine mixture and
perfused. The study was conducted in compliance of the main bioethical
norms. Identification of labeled cells was performed on isolated
preparations of the hippocampus using a click-reaction with azideAlexaFluor 555, stem cells were identified by method of whole mount IHC
with antibodies conjugated with AlexaFluor488. Visualization of the
samples was performed by Olympus FV1000 confocal microscope. Samples
were scanned by the objective with power 20X to the depth of up to 1.5
mm with the step of 5 , and then approximately 25-35 fields were
stitched. 3D reconstructions were plotted based on scanned images.
Using Imaris Bitplane software artificial surfaces of dentate gyrus
were constructed. Together, quantitative analysis of labeled cells was
conducted in specimens.
Methods of IHC and click-reaction providing detection of dividing
and stem cells in whole hippocampus of adult mice were developed. Also
a method of automate EdU+ cells counting using 3D images was processed.
Counting of dividing and stem cells on slices showed that the number of
cells under automate counting was at 30-40% lower than under semiautomate
one.
Using
developed
methods
for
visualization
and
quantification of cells in whole hippocampi specimens, a dramatic
decrease at approximately 75% in EdU positive cells was observed in
those mice which were irradiated with fast neutrons at dose 0.5 Gy
22

(2094.4291.3 for non-irradiated animals and 497.67156.06 for


irradiated animals).
Developed methods allow not only making quantitative analysis of
neurogenesis in whole brain structures, but also can be applied to a
great variety of issues requiring quantitative analysis. Using our
methods we managed to estimate a decrease in dividing cells number in
dentate gyrus of adult transgenic mice caused by irradiation with fast
neutrons.
The study was supported by grant of Russian Government
no.11.G34.31.0071 from 21.10.2011.



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NITRIC OXIDE AND METABOTROPIC GLUTAMATE RECEPTORS IN THE


MECHANISMS OF AUDIOGENIC STRESS
Bashkatova V.G., Vanin A.F., Meldrum B.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
N.N. Semenov Institute of chemical physics Moscow, Russia;
Institute of Psychiatry, Kings College, London, UK
v.bashkatova@nphys.ru
A possible role of novel neuronal messenger nitric oxide in the
genesis of a variety of physiological and pathophysiological processes
was the subject of a number of studies, however the results of these
studies are controversial still now. Both protective and destructive
neurotoxic effects of nitric oxide and its products such as
peroxynitrite were established. A relation of nitric oxide and
neurotransmitter function of glutamate was as the basis for a detailed
study of its possible role in the mechanisms of the processes in which
glutamatergic system of the brain play an important role. It should be
noted that while the study of the relationship of ionotropic glutamate
receptors and nitroergic system in the brain was investigated in a
large amount of work, the problem of possible interaction of
metabotropic glutamate receptors and free radical processes is poorly
understood till our days.
The aim of this work was to study a possible involvement of nitric
oxide as well as metabotropic glutamate receptors in the mechnisms of
24

stress response to sound stimulation in DBA/2 mice with genetically


determined auduogenic reaction. The experiments were carry out in DBA/2
mice. Generation of nitric oxide in mouse brain was measured by
Electron
Paramagnetic
Resonance
spectroscopy
using
diethyldithiocarbamate as nitroxyl radical scavenger. Determination of
lipid peroxidation (LPO) processes in brain tissue was performed by
measuring
thiobarbituric
acid
reactive
substances.
The
sound
stimulation (109 dB for 60 s) in DBA/2 mice normally evoked a wild
running phase usually resulting in clonic- tonic seizure attack. A
significant elevation of nitric oxide generation and LPO content in the
mice brain was found during tonic-clonic seizures in comparison with
control group. Pretreatment with antagonist of the 1st subtype
metabotropic glutamate receptors AIDA at dose 1 mol, i.c.v. completely
suppressed sound-induced seizures as well as the enhanced generation
of nitric oxide and increase of LPO products. The agonist of
metabotropic glutamate receptors of the 1/5 subtypes, DHPG at dose 1
mol, i.c.v., was proconvulsant in DBA/2 mice. Both LPO products as
well as and nitric oxide level in the mice brain enhanced dramatically
during audiogenic seizures.
These findings support the notion that nitric oxide and
metabotropic glutamate receptors might play key role in the mechanisms
of audiogenic stress response in DBA/2 mice.

- -

129SV
..1, .. 1, ..
1

1,2

-
.. , ,
2
,
-, ,
o.burenkova@nphys.ru

,
,
(Francis
et al., 1999; Meaney, 2001; McClelland et al., 2011).
,
(Haggarty, 2009),
. ,

129Sv .

, ,

( ., 2013).
25



129Sv

.
(50 / s.c.)
129Sv (F1) 3- 3-
6- .
.
. F1
(),
(),
- () .
8-
(F2 F3),
F1
F1, .

;
, . 24
,
,

.

129Sv (Vikar et al., 2001; Contet et al., 2001; Rodgers et al., 2002)
.

F1,
,
.
F1

. ,
-
,
. ,
129Sv
F1,
, .
(F2 F3)


F1, -
. ,
F1

-
,

( ., 2013),
( F3).
26


-
.

GENDER-DEPENDENT TRANS-GENERATIONAL EFFECT OF EPIGENETIC


STIMULI ON THE DEVELOPMENT OF THE PHENOTYPE OF 129SV MICE
Burenkova O.V.1, Aleksandrova E.A.1, Zarayskaya I.Yu.1,2
1

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


2
Kurchatov NBIC Centre, Moscow, Russia
o.burenkova@nphys.ru

Effects of the early experiences persist into adult behavior and


are mediated by long-term epigenetic modifications of the expression of
regulatory genes in the nervous system (Francis et al., 1999; Meaney,
2001; McClelland et al., 2011). Administration of histone deacetylase
inhibitors in the early postnatal period increases the level of histone
acetylation in the brain (Haggarty, 2009), and can be a model for such
long-term modification. We have previously shown that multiple
administration of sodium valproate increases the effectiveness of
olfactory learning in male 129Sv mice in early postnatal period.
Observed effects of the histone deacetylase inhibitor administration
was caused by the action of valproate per se since multiple
administration of saline did not improve learning in male pups
(Burenkova et al., 2013).
The aim of this work was to study the effect of histone
deacetylase inhibitor sodium valproate in the early postnatal period on
the behavioral phenotype of adult male 129Sv mice and on the results of
olfactory learning of male pups in the subsequent generations (F2 and
F3).
129Sv mice (F1) of both genders were injected by sodium valproate
(50 mg/kg, s.c.) once on the 3rd postnatal day (PD3) or multiple from
PD3 to PD6. Control animals were given saline using the same protocol.
No administration was performed in the intact group. Adult F1 males of
all groups were consistently tested in the open field (OF), elevated
plus maze (EPM), contextual fear conditioning (CFC), and in the T-maze.
On P8, F2 and F3 pups of both genders obtained by breeding of F1
females of all groups with non-valproate F1 males were trained by
stroking with a paintbrush (that mimics tactile stimulation received
during maternal grooming) in the presence of mint odor (learning group)
or were not exposed to any treatment (control group). All pups were
tested 24 hours later in a two-odor-choice test. The testing camera was
divided into an area containing the conditioned odor (clean shavings
scented with pepermint extract), and an area containing clean shavings.
All procedures were undertaken with the relevant bioethical approvals.
27

Increased anxiety of 129Sv male mice (Vikar et al., 2001; Contet


et al., 2001; Rodgers et al., 2002) was completely confirmed in our
study. Multiple sodium valproate administration in the first postnatal
week has led to the aggravation of anxiety-like behavior of F1 mice
according to time and path length in the central and peripheral zones
of the OF, as well as in the open and closed arms of the EPM.
Contextual testing of F1 males showed no effect of sodium valproate on
the formation of long-term fear memory.
None of the performed during early postnatal period exposure did
not affect the formation of spatial working memory estimated by level
of spontaneous alternation in the T-maze. Therefore, the administration
of sodium valproate to 129Sv male pups did not have long-term effect on
the learning ability of adult F1 mice, however, it led to an increased
level of anxiety.
The results of the olfactory learning of F2 and F3 male pups
showed no effects of multiple administration of histone deacetylase
inhibitor to F1 female pups revealing the absence of prolonged transgenerational effects of sodium valproate administration. In contrast,
multiple administration of saline in the first week of F1 females had
not only direct gender-specific effect, which leads to an improvement
of their own olfactory learning (Burenkova et al., 2013), but also
improved the olfactory learning of their offspring (F3 male pups).
Thus, future research will be required a detailed analysis of
epigenetic modifications in the brain of experimental animals at the
molecular and cellular level.


-
C57BL/6
.., .., ..
-
.. , ,
o.buholtc@nphys.ru
, -
() , 24 ().
,
,
(, , )
.

()
C57Bl/6

()
c-Fos , .
28


. (
19/20/21, 19/24/25, 23/24/25) . 19 23
: 300
, .
20 24
(1 , 2 ),
5 . 24 (21
24) :
300 ,
.
: (/20/21, -/24/25) , (19/-/25, 19/-/25,
23/-/25).
90 (19 23)

c-Fos.
c-Fos
19 23.
. 19/20/21

. 23/24/25 ,
5 , 19/24/25.
c-Fos
19, 24, CA1, CA3
, .
c-Fos 19
, 23.
, ,
, 19 5 .
,
19,
. c-Fos 19
, ,
,
. ,
, ,
21 24,

20
. c-Fos
,
19 23
,
.

29

THE PREEXPOSURE EFFECT ON MEMORY FORMATION IN CONTEXTUAL FEAR


CONDITIONING IN MICE C57BL/6 DURING LATE NESTING PERIOD
Bukhgolts O.I., Ivanova A.A., Zarayskaya I.Yu.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
o.buholtc@nphys.ru
It is now a well-established that contextual fear conditioning
emerges in development not earlier than 24 postnatal day (PND). It is
unknown the immaturity of what brain structures or/and processes of
memory formation causes ineffective learning at early age of
development.
We estimated the age when contextual fear conditioning with
contextual pre-exposure emerges in mice C57Bl/6. Also we investigated
how contextual pre-exposure results in c-Fos expression in hippocampus,
amygdala and prelimbic cortex.
All experiments were conducted according to bioethical rules. Each
mouse underwent three phases as part of contextual fear conditioning:
contextual pre-exposure (phase 1), immediate shock (phase 2) and
testing (phase 3). Pre-exposure was conducted on 19 or 23PND: a mouse
was placed in the apparatus for fear conditioning and could explore the
context during 300 sec. On 20 or 24PND a mouse was presented a single
foot-shock (1 mA, 2 sec). The testing was 24 h after foot-shock. There
were 3 experimental groups (19/20/21, 19/24/25, 23/24/25) and control
groups of each age without pre-exposure (-/20/21, -/24/25) or without
foot-shock (19/-/25, 19/-/25, 23/-/25). 90 min after contextual preexposure brains from some of mice were removed, frozen and cutted. Then
slides were treated for c-Fos immunocytochemistry. To determine the
basal level of c-Fos expression we examined brains which were removed
from mice on 19 and 24PND from home cage.
Our results showed that group 19/20/21 and all control groups
didnt learn fear. The groups 23/24/25 and 19/24/25 freezed
in
testing due to the association between context and shock. Also we found
out that contextual pre-exposure resulted in increase amount of c-Fospositive cells in CA1, CA3 and dentate gyrus and basolateral amygdala
and in the prelimbic cortex. The basal level of c-Fos expression was
significantly higher on 19PND than on 23PND.
So we found out the strong evidence, that contextual memory was
formed on 19PND, but in latent form. The induced c-Fos expression may
show long-term synaptic modifications which represent long-term spatial
memory formation. But the association between context and shock emerges
between 21 and 24PND. It may be possible that interaction between
amygdala and hippocampus is slow to develop or alteration of spatial
memory representation on 20PND. It could be due to slow development of
interaction between amygdala and hippocampus or alteration of spatial
memory representation on 20PND. The high basal level of c-Fos
expression may result from active mature processes in these structures.

30


7-14

.., .., .., ..,
.., ..
, ,
guljamalh@mail.ru


. ,

.
,

, - ,
.
-
,

. -

.
, , -
.
-
. -

. -,
,
, .

I ,
()
- ()

-. II

-.

, III ,

-.
- 7-8 . II

-. 11-12-
31

-
.
13-14
.
,
7-8 9-10- .

BIOELECTRICAL ACTIVITY OF THE BRAIN AND THE SOME VEGETATIVE


FUNCTIONS IN THE CHILDREN OF 7-14-YEAR-OLD AT DIFFERENT
FUNCTIONAL STATES OF WAKEFULNESS
Veliyeva G.J., Hasanova G.A., Ibrahimova A.Sh., Bakhshieva Z.T.,
Kazimov A.H., Ismayilov T.M.
Azerbaijan Medical University, Baku, Azerbaijan
guljamalh@mail.ru
One of the actual problems of the age neurophysiology is the study
of peculiarities of the brain activity and the some vegetative
parameters at various functional states of the different stages of
children development. Thats why the main goal of present work is to
study the states of synchronizing and desynchronizing systems, the
vegetative spheres at various functional states of brain in children of
school age.
Analysis of EEG shows that in the all age group at the state of
relaxed wakefulness the indices of rapid and slow waves had large
evidence in the frontal and alpha-rhythm indices in contrary, in the
occipital zone of both hemispheres. At modeling of intense wakefulness
the tendency to increase the index of beta-rhythm in all zones of
cortex is noted, but authentic increase of this index in the left
occipital zone is observed. In this state alpha-rhythm had tendency to
decrease in the occipital and increase in the frontal. At intense
state from the indices of slow rhythm, in compare with the relaxed, the
authentic decrease of theta-rhythm in the right frontal and increase of
delta-rhythm in the right occipital zone is marked. At emotional
loading in compare with the relaxed state, the increasing of betarhythm index in both in frontal and in the left occipital lobes is
observed. The authentic differences of alpha-rhythm index at modeling
of emotional states were not observed. In compare with the relaxed
state the theta-rhythm index was decreased in the right frontal region
both at negative and positive emotional states.
As the result of analyses of the dynamics of the vegetative
indices at modeling of intense state in children of I age group showed,
the increase of heartbeats rate and increase of
the intensity of
galvanic skin response were positive correlated with the increase of
pulse at ortho-test. In this state in the II age group the increase of
plethysmogram amplitude was negative correlated with the increase of
the pulse at ortho-test.
In the children of elder age groups the
authentic correlation between researched indices didnt reveal, except
the children of III age group, in which the increasing of rate of the
32

heartbeats at intense state with the increase of pulse at ortho-test


was reciprocally connected.
At modeling of negative-emotional state in 7-8-year-old the
positive correlation between the dynamic of rate of heartbeats and
breathing is marked. In the children of II age group the increase of
plethysmogram amplitude was positive correlated with the intensity of
galvanic skin response and negative with the increase of rate of
heartbeats at ortho-test. In 11-12-year-old at the negative-emotional
state the correlation was not observed. In children of 13-14-year-old
the negative correlation between the increasing of heartbeats rate and
dynamic of plethysmogram amplitude is revealed.
The results of analyses of the vegetative indices showed, that
greatest number of correlations at changes of the functional state in
the group of 7-8- and 9-10-year-old children is marked.



:
-
.., ..
-
.. , ,
o.grigorchuk@nphys.ru
: -

( 1) - () ().
: 20 - ,

.
( ).

.
267 (19.06.2003 .),
(
. .. , 1 03.09.2005 .).
: 107
.
23% ,
20% ,
3% .
,
.
.
.
33


-

, .
: ,

-
.
.

.

PATTERNS OF NEURONAL ACTIVITY IN THE DORSAL HIPPOCAMPUS


AFTER STIMULATION OF THE EMOTIOGENIC STRUCTURES OF THE BRAIN
OF RATS WITH DIFFERENT BEHAVIORAL ACTIVITY: DELTA-SLEEP
INDUSING PEPTIDE
Grigorchuk O.S., Umriukhin P.E.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
o.grigorchuk@nphys.ru
The aim of the work: study the effect of the delta-sleep indusing
peptide (DSIP) on activity patterns of the dorsal hippocampus (CA1
field) neurons after stimulation of the emotiogenic and motivational
structures - the ventromedial (VMH) and lateral hypothalamus (LH).
Methods: The experiment was conducted on 10 active and 10 passive
in their behavioral characteristics in the open field test male Wistar.
Stimulating electrodes were in the motivational zones (LH and VMG)
under chloral hydrate anesthesia. Then, the impulse activity of neurons
were recorded under urethane anesthesia. The experiments were carried
out in accordance with the requirements of the order 267 of Russian
Ministry of Health (19.06.2003), as well as with the "Rules of the work
on experimental animals" (PK Anokhin Institute of Normal Physiology
RAMS, protocol number 1 from 03.09. 2005).
Results: 107 neurons of the dorsal hippocampus were registered. After
motivational structures stimulation 23% patterns of the dorsal
hippocampus neuronschanged their patterns of neuronal activity
(20% after LH stimulation, and only 3% after VMH). alterations in the
patterns of the hippocampal neurons were observed in both act and pass
animals only after LH stimulation, but not after VMH stimulation, where
changes appeared only in active rats. After VMH stimulation were only
observed in active animals. Different variants of changing patterns
were detected.
Precursory DSIP application has a modulating effect on the
patterns changes
in the dorsal hippocampus neurons, both the
respondents to the stimulation and the previously irresponsive neurons.
Conclusion: It is shown that the stimulation of the lateral
hypothalamus induces significant reorganization of the hippocampal
neurons patterns, whereas ventromedial hypothalamus stimulation does
34

not. Observed differences in the characteristics of the neuronal


patterns in animals active and passive test in the open field. The DSIP
application before the stimulation has a modulating effect on the
patterns of activity of neurons of the dorsal hippocampus.


-,

..1, ..1, ..2, ..1,
..2, .1
1

-
.. , ,
2
- 170
- , ,
m.gruden@nphys.ru

()
37,2% 40,4% .

.


,

.
,
50 .

,
,
,
-,
. ELISA (n=72) (n=30)
- II, ,
HLDF24, , HLDF, S100b,

, , .

.

,
.
12-06-00709.
35

GENDER AND AGE ASSOCIATED PECULIARITIES IN MOLECULAR


INTEGRATION BETWEEN VASCULAR, NERVOUS AND IMMUNE SYSTEMS IN
NORMAL AND PROGRESSIVE HYPERTENSIVE CONDITIONS
Gruden M.A1, Elistratova E.I.1, Karlina V.P.2, Kudrina M.V.1, Ruzhov
V.M.2,Sherstnev V.V.2
1
2

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


Medical-sanitory department N170 of the Sate Medical-Biological
Agency, Moscow, Russia
m.gruden@nphys.ru

Arterial hypertension (AH) is the most frequent vascular disease


and its distribution in Russia is composing from 37,2% to 40,4%
through male and female population. In present time AH is regarded as
the multifactorial disorder with the different alterations in molecular
mechanisms of blood pressure system. There are data about specific
involvement of the neural and immune protein-peptide
factors in
mechanisms of hypertension development which allow to suggest existing
integration of mentioned above regulative systems with vascular system
on molecular level. Gender and age associated peculiarities of
hypertension prevalence which are manifestimg by significant increasing
of cases in female group after 50 years of age. Searching of consistent
patterns and molecular predictors of hypertension progression is
actual.
Systemic simultaneous study of biomarkers, specific
concentration changes of which are reflected functional state of
vascular, nervous, immune systems in normal conditions and during
hypertension progression and may serve as informative indicator were
carried out. By ELISA in healthy individuals (n=72,age matched control)
and patients with AU (n=30) blood serum in concentrations of peptides angiotensin II, endothelin, HLDF 24, atrial sodium uretic peptide,
proteins HLDF, S100b as also level of idiotypic autoantibodies to all
studied factors as biomarkers of vascular, nervous, immune systems,
respectively. Peculiarities in quantitive content of studied factors
and autoantibody levels to those factors in sera of male and female
patients determined age groups characterized by different blood
pressure statements in normal conditions and with AH were examined.
Positive
and
negative
correlations
between
studied
bionarker
concentrations with clinical indicators of vascular system functional
state in normal and pathological conditions were revealed.
Supported by grant RFH 12-06-00709.

36


CASP3, ASCL1 S100A6

..1, ..1, Sewell R.D.E2., ..1
1

-
.. , ,
2
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff
University, Cardiff, CF10 3NB, U.K
m.gruden@nphys.ru



, ,
..
(Ascl1),
(Casp3, S100a6) ,

Wistar
. , Casp3

Ascl1

1,59
. S100a6
Ascl1
1,55
.
(Casp3/S100a6 )
(Casp3/Ascl1 , S100a6/Ascl1
). ,
-3

.


- ,

.

37

DISTINCT FUNCTIONAL BRAIN REGIONAL INTEGRATION OF CASP3,


ASCL1 AND S100A6 GENE EXPRESSION IN SPATIAL MEMORY
Gruden M. A. 1, Storozheva Z. I. 1, Sewell Robert D. E. 2, Sherstnev
V. V. 1
1

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


2
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff
University, Cardiff, CF10 3NB, U.K.
m.gruden@nphys.ru

Evaluating the brain structural expression of defined genes


involved in basic biological processes of neurogenesis, apoptosis or
neural plasticity may facilitate the understanding of genetic
mechanisms underlying spatial memory. The aim of the present study was
to compare Ascl1, Casp3 and S100a6 gene expression in the hippocampus,
prefrontal cortex and cerebellum of adult rats in water maze spatial
memory performance. After four days training, the mean platform time
(<10 sec) was evidence of stable long-term spatial memory formation.
Real time PCR analysis revealed a positive inter-structural correlation
for S100a6/Casp gene expression between the prefrontal cortex and the
cerebellum but a negative correlation for S100a6/Ascl1 transcribed
genes between the prefrontal cortex and hippocampus during swimming in
the active controls. However, during spatial memory performance there
was only one inter-structural correlation between the prefrontal cortex
and cerebellum with respect to Casp3 expression, though there were
intra-structural correlations between Casp3/Ascl1 transcriptions within
the prefrontal cortex and hippocampus as well as between Ascl1/S100a6
in the cerebellum. In active learners versus naive controls, the
transcrption of all genes was augmented in the prefrontal cortex but
Casp3 and Ascl1 were also elevated in hippocampus whilst only S100a6
increased in the cerebellum. The findings endorsed the role of the
hippocampus in memory acquisition in addition to an integrative
relationship with the prefrontal cortex and cerebellum. This structural
and molecular configuration is important for creation of novel neural
circuitry for consolidation and reconsolidation of memory trace with an
involvement of coupled processes of neurogenesis, apoptosis or neural
plasticity.

38

-

..1, ..1,2, ..1, ..1,
..1
1




, . ,
2
, . ,
gusacova@yandex.ru
,
, ,
,
,
. ,
, ,

().
. :

.


.


.
.
,
,
,
.

.

.
,

.

.
.

39

CYTOSKELETON- DEPENDENT MECHANISMS OF A REGULATION OF


CONTRACTILE ACTIVITY IN SMOOTH MUSCLE CELLS
Gusakova S.V.1, Baskakov M.B.1, 2, Kovalev I.V.1, Birulina Yu.G.1,
Zheludeva A.S.1
1

Siberian State Medical University, Tomsk, Russia


2
Tomsk Polytechnic University, Tomsk, Russia
gusacova@yandex.ru

The ability to maintain a certain shape, and directed to carry out


coordinated movements of cells and organelles is provided by the
cytoskeleton. Main components of the cytoskeleton - actin filaments,
microtubules and intermediate filaments. Recently, there is increasing
evidence that the cytoskeleton may contribute significantly to the
electrogenesis and reduced smooth muscle cells (SMC). Changes in the
state of cytoskeleton elements affect the ion channels and membrane
transporters. Objective: To examine the role of cytoskeletal elements
in the regulation of secondary mediators of electrical and contractile
activity of smooth muscle cells.
We studied smooth muscle segments of the thoracic aorta of rats
and guinea-pig ureter. Amplitude of contractions, recorded as isometric
force tension, was measured as percentage of depolarisation-induced
vascular smooth muscle cells contraction in high-K+ (30 mM KCl) medium.
To study the electrical and contractile activity of the applied method
of the double sucrose bridge. All studies were conducted in compliance
with the basic rules of bioethics.
Revealed that the microfilaments are involved in cytoskeleton
formation starting strain of rat aortic smooth muscle cells are
involved in the generation and maintenance of the contraction induced
by phenylephrine and high-K+ (30 mM KCl) medium. Relaxing effect of
nitric oxide on the depolarized rat aortic smooth muscle cells is
realized
with
the
participation
of
microtubules
cytoskeleton.
Efficiency relaxing effects of nitric oxide in rat aorta smooth muscle
action during phenylephrine depends on the microfilaments and
microtubules cytoskeleton. Found that the contribution of individual
elements in the regulation of cytoskeleton cyclic AMP electrogenesis
and cuts varies in different types of smooth muscles. Implementation of
inhibitory action of cyclic AMP on the contractile activity of rat
aortic smooth muscle cells is carried out with the participation of
microfilaments. In the smooth muscle cells of the ureter effects of
cAMP mediated predominantly microtubules.

40

NOVEL APPROACHES TO THE EXPERIMENTAL MODELING OF


PARKINSONISM: TOXIC - SYNUCLEIN AMULOIDOGENIC SPECIES,
BEHAVIOUR AND AUTOIMMUNE RESPONCES
1

Gruden M.A. ,

Sewell R.D.E., 3Davidova T. V., 3Kucheryanu V. G.,


4
Morozova-Roche L.A.

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


2
Welsh School of Pharmacy, Cardiff University, Cardiff, UK
3
Institute of General Pathology and Pathophysiology RAMS, Moscow,
Russia
Department of Medical Biochemistry and Biophysics, Ume University,
Ume, SE-90187, Sweden

Animal models of Parkinson's disease (PD) have been widely used to


investigate the pathogenesis of this neurodegenerative disorder which
is typically associated with the specific and largely disordered
protein -synuclein (-syn). In the current study, a new Parkinsons
disease model was developed using the nasal vector to deliver -syn
aggregates to the brain. Both -syn oligomers and its fibrils were
firstly characterized using atomic force microscopy and the thioflavin
T binding assay. The toxic oligomers alone (0.48 mg/kg) or their 50:50
combination with fibrils (in a total dose of 0.48 mg/kg) were then
given intranasally for ten days in mice and PD-mimetic symptoms as well
as humoral immunity to these species and dopamine (DA) were evaluated
simultaneously. Open-field behavioral deficits indicated by rigidity
and reduced locomotor activity were induced by the dual administration
of -syn oligomers plus fibrils but not the oligomers by themselves
under the 10-day dosing regimen. In contrast, using ELISA, high levels
of serum autoantibodies to -syn monomeric, oligomeric and fibrillar
conformers as well as DA were observed in both treatment groups
reflecting immune system activation. Thus, nasal administration of syn amyloidogenic species may be a useful experimental PD model which
results not only in motor deficits but also incitement of humoral
protection to mimic the disease. Such a paradigm may be exploitable in
the quest for potential therapeutic strategies and further studies are
warranted.

41

.., .., * .., * ..,


.., * .., .
,
, ,

dav-ta@yandex.ru
,


. ,

,
.
,
, .

.

,
,
, ,
,
.

.

.

.
(ELISA) -
,

(, , )

(,
).

,
. ,

,
,
. ,

,
,
. , ,


, ,
42


,
. ,

.
( 12-06-00673)

NEW APPROACHES TO IMMUNODIAGNOSTIC OF ADDICTIVE BEHAVIOR


Davydova T.V., Vetrile L.A., Nevidimova T.I., Vetlugina T.P., Fomina
V.G., Zakcharova I.A., Batukhtina E.I., Bokhan N.A.
FSBI Institute of General Pathology and Pathophisiology RAMS, Moscow,
FSBI , FSBI Mental Health Research Institute RAMS, Tomsk, Russia
dav-ta@yandex.ru
The search for new approaches to the diagnosis of drug addiction,
alcoholism and other forms of addictive behavior is one of the most
urgent problems of modern medicine. Currently, there is no doubt that
the key role in the mechanisms of addictive behavior plays a
significant restructurization in neurotransmitter systems, namely
neuromediation dopamine in the mesolimbic brain structures. In the
regulation of dopamine neuromediation involved neuropeptides, opioid
system, other neurotransmitter systems. The close relationship and
interaction between the nervous and immune systems requires the active
participation of the immune system in the mechanisms of addictive
behavior. In our studies, and numerous other studies, it is shown that
in narcomania and alcoholism formed secondary immunodeficiency which
characterized by the suppression of cellular immune responses, the
immune response to various antigens, as well as increased production of
autoantibodies to brain-specific antigens and neurotransmitters. The
greatest
interest
in
this
connection
are
autoantibodies
to
neurotransmitters, which are bioregulators of the CNS and the immune
system.
In recent years, much attention is paid to the development of new
molecular techniques immunodiagnostic addictive behavior. Of particular
interest are autoantibodies to neurotransmitters as neuroimmune markers
of addictive behavior . Based on ELISA technique (ELISA) using testantigens dopamine, norepinephrine, and serotonin with bovine serum
albumin
held
immunoassay
changes
in
serum
autoantibodies
to
neurotransmitters (dopamine, norepinephrine, serotonin) at different
periods of addictive behaviors (drug, alcohol).
Specific
serum
patterns
of
autoantibody
detected
to
catecholamines and serotonin, which differ depending on the stage and
duration of remission of the disease.
Antibody level to dopamine,
noradrenaline and serotonin in serum increased in patients suffering
from drug addiction in stage withdrawal and in stage remission compared
with the control group of the same age, having no contact with the
substance. When the patients were in the state of withdrawal at an
acute withdrawal symptoms and abstinence subacute it is found that the
43

level of antibodies to the neurotransmitters dopamine, noradrenaline


and serotonin below in patients with acute abstinence. There is also
evidence
showing
that
the
average
levels
of
antibodies
to
neurotransmitters in patients with episodic substance use is lower than
in the control group, which is important for the early diagnosis of
predisposition to psychoactive substances, including narcotics in young
adults. Autoantibodies to norepinephrine, dopamine and serotonin may
serve as a neuroimmune markers of predisposition to the development of
addictive behavior.
Support by the RNF (Project 12-06-00673).


.
..
, ,
vdemkin@img.ras.ru
:
,
.
.

,
, ,

.
. ,
, ,
,

.
8
5 8 . ,
, ,
, ,
2 , . 5
( L.iners L.jensenii L.
crispatus, L. gasseri, L. johnsonii)
5 139 . ,
16S 23S
, 124 ,
, .

M.hominis
M.genitalium.
665 .
M.hominis
580 . M.genitalium.
, ,
44

. 16
, 3 .
Gardnerella vaginalis, Atopobium
vaginae A.parvulum 244
, 42 .
2
. G. vaginalis
A. vaginae,
A.parvulum 38 .

- ,
,

,
G.
vaginalis.

,

.
. ,
, , ,
.
Chlamydiaceae.

.

, .

SEARCHING FOR MARKER SEQUENCES IN THE GENOMES OF BACTERIA FOR


THE DEVELOPMENT OF SYSTEMS FOR ANALYSIS OF HUMAN MICROBIOTAS.
Demkin V.V.
Institute of Molecular Genetics of RAS, Moscow, Russia
vdemkin@img.ras.ru
Objectives: searching for new genetic targets and markers for
identification and differentiation of bacteria composing human vaginal
microflora.
Methods. Computer analysis of DNA sequences, multiple alignments
of nucleotide sequences, computer design of primers and probes, nucleic
acid amplification with different principles of fluorescent signal
generation and detection in real time were used.
Results. A comparative analysis of genomes of chlamydia,
lactobacilli, genital mycoplasmas and other bacteria, which are
components of the human vaginal microbiota, to search for conserved
regions that have generic-and species-specific traits has been
conducted.
In the analysis of the genomes of eight species of Chlamydiaceae,
consensus motifs in 5 genes and 8 intergenic regions were identified.
Unlike chlamydiae, lactobacilli have more species, wider distributed in
nature, and have a genome, which is almost two times higher in
lactobacilli than in chlamydiae. Comparison of the genomes of five
species of lactobacilli: large fragments of L.iners and L.jensenii and

45

full genomes L. crispatus, L. gasseri, L. Johnsonii,


revealed
homologous motives for all five species studied in 139 genes.
As in the case of chlamydiae, the largest proportion of homologous
regions accounted for the genes 16S , 23S rRNA and tRNA, but the 124
genetic regions having consensus motives in all the tested
Lactobacillus species were not related to the rRNA and tRNA genes.
A comparative genomic
analysis of two genital mycoplasmas M.hominis and M.genitalium has been conducted. Mycoplasma genomes are
the smallest ones among of cellular organisms and it is 665 thousand
base pairs for M.hominis and 580 million base pairs for M.genitalium.
Despite the fact that both species are members of the same genera, they
have very low degree of homology. There were found 16 homologous
motives, of which only three encoded protein products.
By comparative analysis of the genomes of Gardnerella vaginalis,
Atopobium vaginae and A.parvulum a total of 244 motives were
identified, of which only 42 were common to all three species. Of
these, only two were not related to the ribosomal or transport RNA
genes. 38 motives were common to G. vaginalis and A. vaginae, but were
absent in A.parvulum.
Based on real-time PCR technology with Taqman probes, candidate
systems for determining chlamydiae, lactobacilli, genital mycoplasmas,
G. vaginalis have been developed. These microorganisms are the most
common species in human vaginal microbiota at defined pathological or
borderline states.
Conclusions. New genetic targets that can serve as genetic markers
of chlamydiae, lactobacilli, genital mycoplasmas, gardnerellas were
identified. For the first at the genomic level, all the conserved
consensus genomic sites of bacteria of the family Chlamydiaceae have
been determined. These sites can serve as genetic markers and can be
used to develop systems for detecting and genotyping for this group of
bacteria. Candidate multiplex systems for determining the different
bacterial species constituting the human vaginal microbiota have been
developed.

46




.., .., .., ..
. .. , .
,
dorofov@mail.ru

()

.

42

18 20 .

- .
,
.
.

3 :
21 ;
17 ;
4 .


, ,
, , VLF LF/HF.

,
- .

,
LF ( = 0,02) LF/HF ( = 0,04).

: ( = 0,01), ( = 0,03),
: ( = 0,02).


.

.


.
, -
, - .

-
47


.


. ,


.

ROLE OF SPELEOCLIMATOTHERAPY IN THE DEVELOPMENT


OF THE AUTONOMIC NERVOUS SYSTEM ADAPTIVE REACTIONS IN
HEALTHY INDIVIDUALS, DEPENDING ON THE LEVEL OF TRAIT ANXIETY
Dorohov E.V., Gorbatenko N.P., Karpova A.V., Semiletova V.A.
Voronezh State Medical Academy named N.N. Burdenko. Voronezh, Russia
dorofov@mail.ru

The aim of this study was to investigate the effect of correcting


features of speleoclimatotherapy (SCT) on the performance of vegetative
homeostasis of students depending on the level of trait anxiety.
The study involved 42 students of the Voronezh State Medical
Academy at the age of 18 - 20 years. The study evaluated the
performance of heart rate variability and trait anxiety on the
Spielberg-Khanin. All study students passed the course of SCT, which
was ten two-hour sessions in the afternoon at one and the same time.
All study participants gave written informed consent to participate in
the study.
Students were divided into three groups on the basis of baseline
trait anxiety: with high levels of trait anxiety - 21 students, with an
average level of trait anxiety - 17 students, with a low level of trait
anxiety - 4 students.
Students with high and medium level of trait anxiety in terms of
heart rate variability observed activation of the sympathetic division
of the ANS, which was reflected in the higher relative to age norms,
indicators of AMo, VLF and LF/HF. In the group with low levels of trait
anxiety students in terms of vegetative homeostasis are characterized
by normotonia with high TP, reflecting the adaptability of the
cardiovascular system.
The students with high levels of anxiety: activity of the
sympathetic division of the ANS is intensified during the course of SCT
(LF (p = 0.02) and LF / HF (p = 0.04)). Students with normal levels of
anxiety after a course of SCT:
activity of the sympathetic division
of the ANS was decreased (AMo (p = 0.01), MI (p = 0.03)), as well as
activity of parasympathetic ANS was increased (BP (p = 0.02)). In the
group of students with low trait anxiety indicators of heart rate
variability did not change significantly during the course of ACT.
Thus, the mechanism of speleoclimatotherapy action contributes to
the development of the phenomenon of long-term adaptation. The specific
48

micro-climatic factors contribute to the development of the general


adaptation syndrome and affect to the organism of healthy man on the
mechanism of pessimum strength of the stimulus. Positive corrective
effect of SCT is possible only if the compensatory-adaptive body
reserves are exhausted, as shown in students with normal and vagotonia.
With initially normal levels of trait anxiety action of ACT was
associated with decreased activity of the excess stress implementing
systems in the process of adaptation to microclimate speleological
chamber; and the phenomenon of "cross-resistance" is developed. In
individuals with high levels of trait anxiety activity of the
sympathetic division of the ANS is increased and it is associated with
impairment of functional capacity of the organism for correcting the
impact of these structures. Consequently, the initial high level of
trait anxiety in conjunction with sympathicotonia leads to disadaptive
violations due to the impact of factors of SCT.




.., .., .., .., ..,
.., .., ..
, , ,
zvv@pharm.tsu.ru


. ,

,

.
(),

.
: -
,


.
:
( );
,

Cl4;

,
; ,
, .
,

49

IACUC. ,
,
,
,
.
. ,
, ,
, -,
, ,
.

-,

,
. ,

, ,

.

()

, -.

.
,

.
:

-
.

2009-2013

( 02.740.11.0781)
2020
( 16.N08.12.1008).

MECHANISMS OF PROGENITOR CELLS CONTROL AS TARGETS FOR DRUGS


OF PHARMACOTHERAPY OF DEGENERATIVE DISEASES
Dygay A.M., Zhdanov V.V., Zyuzkov G.N., Udut E.V., Miroshnichenko
L.A., Skurihin E.G., Pershyna O.V., Minakova M.Yu.
FSBI Research Institute of Pharmacology SB RAMS, Tomsk, Russia
zvv@pharm.tsu.ru
Accumulation of data about functional properties of stem cells
resulted in the development of a new direction in the treatment of many
diseases - cell therapy. In our opinion, the most physiological
approach to solving problems of the regenerative medicine is the
pharmacological management of the functions of endogenous stem cells,
based on the principle of imitating the activity of the natural
50

regulatory systems in the organism. Mesenchymal stem cells (MSCs),


which are able to differentiate in the cells of various tissues due to
high degree of their plasticity, are the optimal target for this
purpose.
Research objective: To study the role of mesenchymal progenitor
cells in the development of pathological processes, mechanisms of their
regulation and development of pathogenetically substantiated methods of
pharmacological stimulation of their mobilization and differentiation
in the tissue-specific progenitors on models of some common diseases.
Methods. Studies were carried out on experimental models of
myocardial infarction (left coronary artery ligation); toxic hepatitis,
induced by CCl4 administration; diabetes caused by alloxan; hypoxic
encephalopathy; bleomycin-induced pulmonary fibrosis, as well as on a
model of persistent cutaneous wound. All experiments were conducted in
accordance with the rules adopted by the European Convention for the
protection of vertebrate animals after the approval of the research
program
by
IACUC.
Cultural,
biochemical,
immunological,
electrophysiological and morphological methods were used in the study.
Results. Analysis of the results, received on various models of
pathological processes, showed that changes in the reserve systems of
cellular renewal prove to be similar and nonspecific in spite of some
characteristic features that are determined by the nature of acting
pathogenic factor. However, in most cases, activation of bone marrow
stem cells appeared to be insufficient to compensate existing damages.
Course administration of G-CSF mobilizing mesenchymal stem cells
contributed to more full realization of their regenerative potential.
After stimulated release from the depot, migration and homing
mesenchymal progenitors differentiated in the working tissue of
corresponding organ or in the microenvironment elements, which
indirectly accelerate the course of reparative processes of damaged
tissues. The use of hyaluronidase (imHD) immobilized on different
polymers
led
to
sequential
stimulation
of
proliferation
and
differentiation of both regional stem cells of different organs and
progenitor elements of tissue-depot. In the last case, their activation
was accompanied by their maximally directional migration in the
affected organs. Mechanisms of imHD action are not only influence on
the extracellular matrix, but also its effect on the secretory and
adhesive functions of microenvironment cell elements.
Conclusions: The obtained results show the principal possibility
and prospects of the pharmacological modification of various endogenous
progenitor cells functions by impact on the activity of the natural
regulatory systems in the organism
This work was supported by grants from the Federal Target Program
Research and scientific-pedagogical personnel of innovative Russia for
2009-2013 (State Contract 02.740.11.0781) and the Federal Target
Program Development of the Pharmaceutical and Medical Industry of the
Russian
Federation
for
the
period
up
to
2020
and
further
prospect(State Contract 16.N08.12.1008).

51

ORTHOSTATIC CARDIOVASCULAR RESPONSES, EMOTION REGULATION AND


STRESS-COPING MECHANISMS
Davydov Dmitry M.

1,2

, Ra Czabak-Garbacz3, Magdalena Koscik3

Institute of General Pathology and Pathophysiology, RAMS


P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
d.m.davydov@gmail.com
3
Department of Human Physiology, Medical University of Lublin, ul.
Radziwiowska 11, 20-080, Lublin, Poland
czabak@am.lublin.pl
2

Previous studies have suggested that systolic blood pressure (SBP)


responses to orthostatic challenge are able to indicate a resilience
capacity against a mood disorder after adversity, but have not
designated stress-coping and emotion regulation mechanisms mediating
this relationship. The present study was conducted to investigate
relationships between the orthostatic SBP responses and different
styles of coping with external (adversity) and internal (illness)
problems, which are able to be such mediators. Four readings of early,
mid, and late SBP responses to lying down followed by similar 4 SBP
readings after standing up were obtained from 47 healthy students (26
women) along with later estimations of their emotional control, life
orientation, self-efficacy, emotion-, task-, and avoidance-coping
strategies, health-related locus of control, and illness acceptance, as
well as their negative and positive mood levels. Profile analyses
(adjusted for sex, age, and BMI) showed that (i) SBP increase from midto late-period after lying down was significantly related to low
satisfaction with life in contrast to SBP decrease associated with high
life-satisfaction, (ii) SBP decrease during a posture change from lying
to standing was significantly related to a lower self-belief (i.e.,
pessimistic view) in coping with adversity, and a higher control of
negative mood in general and a depressed mood, in particular, whilst
SBP increase was associated with the opposite coping styles, (iii) a
lower SBP level in late phase of standing compared to late phase of
lying was related to low scores of happy mood and avoidance coping
strategy, whilst the opposite SBP profile was associated with high
scores of the psychological measures. The findings suggest that lower
SBP during lying and higher SBP during standing are related to several
coping mechanisms which protect positive subjects mood and optimistic
view on life. Thus SBP response to orthostatic (posture) change (a
gravity induced, biological challenge that triggers several successive
evolutionary-developed physiological adaptive processes) can also
indicate individual coping styles, which humans apply for to support
individual resilience against psychosocial stressors.

52



.., ..
-
.. , ,
, ;

, ; - , ,
o.efimova@nphys.ru

.


, .

(., 3DISCO, Scale, CLARITY).
,
.

LUMOS
(LUminocity
Maintaining
Opticlearing
Solution). LUMOS

(, , .)
.
,
, LUMOS
, .
LUMOS
1 .
LUMOS, ,
2

.
,

Thy1-EGFP Brainbow,

GFP,
,
c-Fos-GFP Zif/268-GFP
,
- .
,
LUMOS

,

.
11.G.34.34.31.0071.

53

A NEW OPTICAL CLEARING SOLUTION


FOR 3D FLUORESCENT IMAGING
Efimova O. I., Anokhin K. V.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
Natl. Res. Ctr. Kurchatov Inst., Moscow, Russian Federation
Moscow Inst. of Physics and Technol., Moscow, Russian Federation
o.efimova@nphys.ru
Development of new 3D imaging methods for visualization of whole
organs at cellular resolution should have a significant impact on
neuroscience
research
and
biomedical
diagnostics.
Microscopic
visualization of entire neuronal networks in unsectioned brain
specimens requires their optical transparency and preservation of their
three-dimensional structure and fine morphology. A number of approaches
have been recently developed to obtain optically transparent biological
samples, including 3DISCO, Scale and CLARITY. However, each of these
techniques has certain limitations. To address these problems, we
developed a new clearing agent termed LUMOS (LUminocity Maintaining
Opticlearing Solution). LUMOS enables fast three-dimensional optical
imaging of genetically encoded fluorescent proteins in brain structures
(e.g. hippocampus, neocortex, olfactory bulb) from the fixed adult
brain. Unlike other clearing methods which may be compromised from
shrinkage or expansion of the biological sample, the water-based LUMOS
does not cause distortion of the tissue and retains its native threedimensional information. LUMOS preserves fluorescent signals of
reporter proteins in the intact structures for at least 1 year. Twostep low-cost LUMOS clearing procedure requires less than two days and
renders brain structures uniformly transparent, allowing their
subsequent 3D microscopy with cellular resolution and automatic
counting of fluorescently labeled targets. We have shown that this
approach enables imaging of the entire neocortex and hippocampus of
adult Thy1-EGFP and Brainbow mice. It also allows three-dimensional
localization of GFP-encoding viral vector transduced into the mouse
brain as well as fast quantitation of experience-induced expression of
c-Fos-GFP and Zif/268-GFP in neurons of entire olfactory bulbs,
cerebral cortex and hippocampi after fear conditioning in mice. Thus
LUMOS enables high-throughput 3D fluorescent analysis of brain
structures at cellular resolution which may shed light on the structure
and functions of large neuronal circuits.
Supported by Russian Government grant 11.G.34.34.31.0071.

54


-
.., ..
-
.. , ,
b.zhuravlev@nphys.ru

(17 , 18-22 )
-

. ,
% ,
,
, 70%
35% . ,

. -2
, .
-1
: ,
. -2

, .

: ,
.
-

.


.

- . ,
,
- , ,

,
, ..
.

55

THE NEUROPHYSIOLOGICAL ANALYSIS IN THE CONDITIONS OF


NOVELTY DURING THE HUMAN SENSO-MOTOR TESTING
Zhuravlev B.V., Murtazina E.P.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
b.zhuravlev@nphys.ru
The study of behavioral and electroencephalographic indices in
humans (17 volunteers, 18-22 years of age) during the execution of a
complex sensorimotor activities in terms of bringing novelty
situational parameters and launch incentives to develop skills
background. As a result of the survey revealed that the majority of
subjects there was a decrease % hit, impact the score, the resistance
to the processes of mismatching, but the increasing level of riskiness
in 70% and the stability in 35% of subjects. It was found that the
novelty of the test compared with the automated activity causes a
decrease in the EEG theta rhythm in many areas of the cortex of the
left hemisphere of the brain of the subjects. EEG alpha-1 range rate is
not changed. The spectral power of the alpha-2 rhythm symmetrically
decreased in all regions except the frontal zone of the right
hemisphere. The picture changes in the spectral power of rhythm beta-1
band EEG was not clear: it increases observed in the right parietal
area, and decrease - in the left frontal and visual areas. Beta-2 EEG
rhythm largely symmetrically increased in the central areas, and
particularly the parietal cortex, and the left visual field. Indicators
of full coherence of the rhythmic activity of inter-hemispheric leads
increased with the implementation of a series of tests in the new
environment: between frontal, parietal and visual areas of the cerebral
cortex of subjects. Analysis of intra-hemispheric coherence of the EEG
rhythms revealed a greater degree of increase linkages in the right
hemisphere of the brain. Identified specific patterns increase the
coherence of the activity areas of the cerebral cortex in different
frequency bands of EEG rhythms. A significant relationships between
changes in performance, in terms of novelty of the test with changes in
the spectral characteristics of coherent EEG persons surveyed on
indicators by the previous test series. Thus, the results of the
analysis of electroencephalographic parameters during the execution of
sensorimotor activity in the new conditions showed that the degree of
change in the spectral characteristics of EEG coherence, in particular,
changes in hemispheric and intrahemispheric performance synchronization
activity of different cortical areas of the brain can determine the
rate of re-education and human the nature of its activities, ie
adaptability to changes in the conditions of the subject results.

56



..

..., ,
vzilov@yandex.ru

,
(subtle) .
,
,

(Gerber R.,1988).

. ,
/

,
,

,
(Bellavite P.,Signorini A.,1984).

,
, ,
.
,

()
.
()
. ,


.
, ,
,
( ., 2010).
().

( 180
.) .
,

.( .., 2012).


57

: , . ,
, , ,
,
, ,
.

ENERGY AND INFORMATION IN CURATIVE MECHANISMS OF SOME


NONCONVENTIONAL THERAPIES.
Zilov V.G.
I.M.Sechenov First Moscow state medical university, Moscow, Russia
vzilov@yandex.ru
Electromagnetic fields analysis of an organism which was named as
subtle energy is one of the interest of contemporary researchers. Due
to those investigations the concept of so called vibrational medicine
was postulated. According to that concept the human being is presented
as a multidimentional organism made up physical/cellular systems in
dynamic interplay with complex regulatory energetic fields (Gerber
R.,1988). Vibrational medicine with its energy was proposed and was
demonstrated to treat human beings instead of conventional drug and
surgery technologies.At the same time energy manifestations were found
to be in close relationships with informational processes to maintain
homeostasis of an organism. Notion that disease is a result not only
disturbances
in
structures
and/or
in
functions
with
various
pathological manifestations but also is considered now as an
informational disorder or 'disorganization (Bellavite P., Signorini
A., 1984).
Thus the assumption that integration of variuos energy/information
methods together with pharmacotherapy to enhance the treatment
efficiency seems to be real.
The effectiveness of acupuncture to normalize energy exchange of
an organism which was spoiled by pathology is proved in numerous
investigations in spite of vagueness in concrete curative mechanisms.
Positive role of energy and information in treatment when high
dilutions are used in homeopathy is demonstrated. Curative activity of
homeophatic remedies as a result of electromagnetic waves shift against
the waves of xenobiotics is shown in contemporary observations
(Komissarenko A., 2010). Energy and information are considered to be
the basis for bioresonance therapy (BRT). An 180 degrees in phase
inversion of electromagnetic waves coming to BRT apparatus from an
organism with its following return to the patient is found to abolish
the
pathological
oscilations
and
to
intensify
the
proper
physiological ones.(Gotovsky M, 2012).
The
homeostatic
triangle:
'substance,
energy
and
information has to be considered when final curative effect of
acupuncture, homeopathy and BRT to normalize extracellular matrix
touched by disease is analyzed.

58

-

.., ..
. .. ,
,
Odonata1108@yandex.ru
()
- (),
.

. , ,

.

. .. . 183 ,
, , -
.
.

(),
( )
. (),

-.
.
-
, 32,2 %

19,2
%

, 48,6% . ,
.


. , 43%
(), 49% , 8% . 70,8%
, ,
() , 4,5%.
48%, 44%, 8%
. 30,5%
, 56% ,
9% . 48,5%
,
. 57% , 43% .
,
.

, .
,
59

.

. ,

.
, -

.

FEATURES OF STUDENTS PSYCHO-EMOTIONAL STATUS CONSIDERING


ACTIVITY OF AUTONOMIC NERVOUS SYSTEM
Zinchenko E.M., Lykova E.U.
Saratov State University of N.G.Chernyshevsky, Saratov, Russia
Odonata1108@yandex.ru
The autonomic nervous system (ANS) actively participates in
processes of adaptation due to the influence on the cardiovascular
system (CVS), which has a subtle and sensitive apparatus of selfregulation. Also, in the earlier studies, an association between the
human psyche and physical reactions has been educed. But considering
the ambiguity of this connection, the purpose of the study was to
examine the emotional state of students taking into account vegetative
state.
The study was conducted in Saratov State University named after
N.G. Chernyshevsky. 183 students who study at the biological, chemical,
mechanical, mathematical and historical faculties were examined. The
study was conducted in the first half of the day in the middle of the
week. All the testees heart rate (HR) was recorded by palpation,
systolic and diastolic blood pressure (SBP and DBP) was determined by
the method of Korotkov in the sitting position at rest. Then Kerdo
vegetative index (VIK), which reflects the relationship between
sympathetic and parasympathetic ANS was calculated. Evaluation of
mental and emotional status of students was made with using the test
questionnaires of
SAN and Spielberger Hanin. All obtained data was
subjected to statistical analysis.
The assessment of neuro-vegetative status of students in terms of
PEC revealed that 32.2% of examinees have dominated sympathetic impact
on the cardiovascular system, 19.2% - parasympathetic, while 48.6% amphotonic. Consequently, most people have a balanced influence of ANS
on CVS.
Determination of psycho-physiological characteristics showed that
students with different vegetative status differ in their level of
anxiety. Thus, 43% of students with Ayton have got moderate personal
anxiety (PA), and 49% - high, 8% - low. 70.8% of these people calmly
react to the situation, but there are students whose reactive anxiety
(RA) is high, the figure is 4.5%. Moderate LT was detected in 48%, high
in 44%, low in 8% of participants with increased excitability of the
sympathetic centers. 30.5% of students are characterized by moderate
60

stress and anxiety, 56% have got low RA, the number of people with a
high TA has increased by 9 %. 48.5% of examinees with a predominance
of parasympathetic have moderate RA, other participants have high RA.
57% of examinees have low RT, 43% have moderate RA. Consequently,
students with Ayton and sympathicotonia are more balanced.
SAN test results indicate the variability of health, activity and
mood of the patients. The majority of students with different
vegetative assess their health status, activity and mood as average or
above average. The highest estimates in terms of "health" and "mood"
were given to students with sympathicotonia. Consequently, the psychoemotional status of the majority of the test matches to a normal and
it is better in representatives with a predominance of sympathetic
department.
Thus, it is necessary to take into account individual personality
characteristics of students and their vegetative state in order to
increase a learning efficiency.




..
... , . ,
hismilova@azdata.net

()
.
-
,
50 .
,
.

,
- -
, , , 10-
,
.

.

.
, ,
( 25 / 1
61

, )



-
- . ,
(500 )
, ,
. ,
(50 ) , ,
,


.
..,

- - .
,

,
( )
.
,

.
,

,


.

ROLE OF BRAIN SEROTONERGIC SYSTEM IN THE MECHANISMS OF


REALIZATION ACCEPTOR OF ACTION RESULT IN BEHAVIORAL CONTRAST
MODEL IN RATS
Ismailova Kh.Yu.
Institute of Physiology n.a. A.I.Karaev Azerbaijan National Academy of
Sciences, Baku, Azerbaycan
hismilova@azdata.net
The goal of this work was study of the peculiarities of the effect
of serotonin selective reuptake inhibitor fluoxetin on the realization
of conditioning food reactions (CFR) in male Wistar rats on emotionally
different background.
The animals acquired the
conditioned running reaction to the
shelf placed in the special chamber of the experimental box where bread
balls of 50 mg were used as a reinforcement. Opening the door which
separated the start and goal chambers of the box served as a
conditioned stimulus. For the purpose of evaluation of the effects of
62

emotional status on the conditioned reflex realization a behavioural


contrast method was applied which allows emotional-positive and
emotional-negative
status
within
the
same
modality
of
food
reinforcement to be formed which are due to tenfold increase or
decrease of the original food reinforcement value used in CFR
formation. Changes in the reinforcement in food value resulted in
changing in the goal-directed reaction time toward decreasing or
increasing. The experiments were conducted in conformity with the
international and domestic rules of humanistic treatment with animals
and were confirmed by proper committee of the Institute.
The data analysis indicate that the animals which were given
fluoxetin (25 mg/kg of animals weight into the stomach by iron tubing 1
hour prior to experiment; the control animals were given distilled
water) were characterized by adequate reaction to the sharp changes in
food reinforcement amount as appropriate changes in the performance of
conditioning reflex rate under emotionally-positive and emotionallynegative states. In particular, time of performance of CFR in rats
received fluoxetin did not differ from that of control animals under
sharp increase of food amount (500 mg). On the other hand, in the rats
received fluoxetin sharp reduction of food value (50 mg) caused slowing
of CFR performance as compared to the control animals accompanied by
increasing of the numbers of groomings and rearings and transforming
to development of frustration reaction as refusal of performance of
formed food reaction.
According to P.K.Anokhins functional system theory reversal
afferentation on completed behavioural act and comparison it to
acceptor of action result determines not only successfulness of
adaptive
reaction, but as well manifestation of accompanying
emotionally-positive and emotionally-negative states. It has been shown
that reinforcement by decreased food amount on the fluoxetine
background causes disconformity in the acceptor of action result and
followed by negative physiological reactions in the animals (anxiety)
and total refusal of positive conditioning reflex reflex performance.
The
literature
data
has
emphasized
the
role
of
brain
serotoninergic system in the anxiety mechanism. Fluoxetin by increasing
the serotonin level in the neuronal terminals and changing animals
emotional state influences their behaviour within the frames of already
formed acceptor of action result.

63



.., ..
, ,
, ,
kapil@yandex.ru

.
60 - 18-22
. :
,
, .



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64

,
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)

.
.

PHYSIOLOGICAL MECHANISMS OF COORDINATION OF MOVEMENT OF


ATHLETES IN UNSUPPORTED POSITION
Kapilevich LV, Koshelskaya EV
Tomsk Polytechnic University, Tomsk State University, Tomsk, Russia,
kapil@yandex.ru
In work on the basis of a comparison of published data and the
results of their research analyzed the physiological mechanisms of
coordination in the support-free status in athletes. Were examined 60
male volleyball players aged 18-22 years of different skills. Methods:
Digital stereophotoregistration movements athlete and ball flight with
a computer image analysis, electromyography, computer stabilography.
Computed stabilography method it was found that the formation
ability to maintain balance and coordination shown in the predominance
deviations from the vertical axis in the sagittal plane decrease in
linear velocity oscillations common center of gravity (CCG) and
coefficient of asymmetry. Qualified athletes in the preparatory phase
of CCG held in the rest position, and then CCG moves forward on the
path of impact and returns. Deviation to the right side is marked only
after contact with the ball and is a consequence of the inertial
movement of the right hand. Novice volleyball players already in the
preparatory phase commit move CC ago. At the time of the kick curved
trajectory of the CCG, which significantly reduces the efficiency of
the movement. In the final phase for balance athletes perform
oscillatory movements in both directions.
Electromyography method showed that there are significant
differences in the organization of the different muscle groups.
Athletes unskilled all the muscle groups involved in the reduction of
time and the duration of the active phase of the flexor and extensor
muscles differ slightly. The second phase elbow flexor carpi negligible
in magnitude and duration, reflecting the weak involvement of the brush
movement in the final phase - the main contribution to its
implementation makes movement of the elbow.
Phase activity triceps
muscle is much longer in highly skilled volleyball, and elbow flexor
65

carpi observed two flash, and the amplitude of the second is much
higher than the former. This reflects the involvement of the brush into
the final phase of shock movement.
The results indicate the existence of fundamental differences in
the technique of execution of direct attacking shot beginners and
skilled players volleyball teams. The differences are related to the
coordination of the first movement of the trunk and arms in the phase
of flight, and secondly, to the organization of muscle beating hand and
third, the nature of the movement of CCG of athlete.
For many team sports are the most typical precision-target species
movements performed in the unsupported position. It is shown that the
conditions of the movement depends on the nature of the prevailing
mechanisms are implemented with the participation of their regulation.
Mechanism for the regulation of movements a support was
associated
with the optimization of the structure of the motor act. Basic
mechanisms of forming coordination abilities in these conditions are
associated with the vestibular analyzer. In the unsupported position
(when performing a jump shot) reduction of impulses from the vestibular
apparatus is compensated by the increased influence of the second type
of postural reflexes - tonic neck reflex, which are activated by muscle
spindles of the neck muscles. Formation of coordination abilities in
such circumstances is the slowest and requires special effort.


..
High Technical Institute of Kozani, Greece
-
.. , ,
lamarakel@gmail.com

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66

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67

THE PRINCIPLE OF DUALITY IN THE WORK OF THE FUNCTIONAL


SYSTEMS
Kelesheva L.F..
High Technical Institute of Kozani, Greece
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
lamarakel@gmail.com
It was suggested the principle of duality and unity in the
activity of the functional systems of organism (FUS).
The interaction of polar things as a dualism and dichotomy
responsible for development and for a driving force of self-control and
self development have ancient beginnings: Geb and Hut for Egyptians, Ki
and An for Sumer, Prakriti and Purusha for Indians, In and Ian for
Chinese. The ideas of duality and unity of the living systems are
traced in ancient Greek philosophy of Anaximenes, Heraclitus and Plato,
in the works of Descartes, Schelling, Kant, Hegel, Lewie de Broile,
Bogdanov and others. Opponents of P.K. Anokhins theory of FUS, who
suppose, that the activity of FUS is started with deviation of result
from a physiological value and completed passively with his return in
the norm, exposed, ungrounded in our opinion, to criticism the theory
of FUS because, as they say, one of the fundamental philosophical laws
- the law of unity and fight of oppositions is not reflected in this
theory.
It is known that the systemogenetic factor of any orders FUS is a
deviation of some parameters of organism activity from the certain
comfort physiological zones of oscillation, inherent for any living
non-equilibrium
open
system,
characterized
by
maintenance
of
homoeostasis. Obviously, that the deviation from comfort zones has
ambivalent character, because can be both toward a decline and toward
the increase of parameters, i.e. a result in it self can have opposite
signs. The return of rejections to the zone of comfort deviations is
realized through the mechanisms of negative feed back by the initiation
of the activity of chains of FUS, that, depending on sign of
deviations, may be differently directed and frequently have straight
opposite action on the same parameter . Reduction of the managed
parameter, for example, the decrease of blood pH, the temperature of
body or level of Ca over some limit provokes step-up influence from the
side of the subsystem attended with the parameter; its sharp increase
stipulate opposite influence. Regardless of polarity of rejections of
physiological parameters, as a result of cooperation and co-assistance
of different and, often, differently directed chains of FUS the final
useful adaptive result namely a return of physiological parameters to
optimal comfort for stability of organisms values, is arrived at.
At the same time, all, even the hardest, parameters of
homoeostasis have a certain range of deviations within the limits of
comfort for normal existence values. We suppose that deviations of
parameters in these limits, carrying opposite character also, are
regulated with the use of positive feed-backs providing further
deviation of parameter from a primary value. For example, eating and
68

its receipt in a stomach strengthen the secretion of gastric juice


necessary for the hydrolysis of food, and the products of hydrolysis
stimulate in turn the intestinal secretion, that accelerates and
strengthens the further overcooking of food. But with the attainment of
a certain level of nutritives, the mechanism of negative feed-back of
the nutrition FUS system is activated
in the organism, resulting in
its stabilization. Positive feed-backs play a special role for a height
and development, for appearance of new internals leading to the
increase of complexity and variety of organisms, i.e. to the selforganization and self-development.
Thus, the principle of duality and integrity in regulation of an
organisms functions is reflected in the dynamic cooperation and coassistance of the differently directed elements into unique FUS on the
basis of permanent analysis of negative and positive feed-backs,
provoked by the different on a sign result of action.



..
-
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klassina@mail.ru




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14 19-32
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max=220- (), %= 100%*i / max,
= ( ..)* (/) / 100 (.).

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69

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SYSTEMOQUANT'S PARAMETERS AS A CHARACTERISTIC OF THE MAN


SPORT ACTIVITY MECHANISM FUNCTIONING
Klassina S.Ya.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
klassina@mail.ru
The aim of this study was to investigate systemic mechanisms for
the sportsmen training activity on the treadmill in the phasingincreasing dose process of physical activity.
14 sportsmen aged from 19 to 32 years were involved in the
experiment. R. Bruce load testing protocol has 9 stages load, and it
was used. In a background and on each of 9 stages load testing
70

registered an electrocardiogram and measured the blood pressure (mm


Hg). On their basis estimated the current value HRi (beats/min),
HRmax=220-age (year), %HR = 100%*HRi / HRmax, Robinson's index DP = ADS
(mm hg) *HR (beats/min) / 100 (.). Before testing all sportsmen were
estimated for motivation level. Methodological base of this study was
the concept of system quantization of behavior (K.V.Sudakov), according
to which achievement of the final result of a systemoquant (performance
of all 9 stages of loading) has happened step by step from a stage to
a stage. Each stage result was characterized by the parameter (load
capacity of a stage, MET) and had the "the physiological price" (%HR).
This study is performed with observance of bioethical standards.
Results: The central question of such system research is to
identify the relationship between systemic categories: motivation
parameter of result "the physiological price" of result. The
systemoquant of sport activity
could be described in these terms
(or parameters) also.
The
motivation level influences on "the physiological price"
of result reached by it. It is revealed, that the maximum "the
physiological price" for the final result was "paid" by sportsmen, who
had the average level of motivation, while "the physiological price"
was lower for sportsman, which had the level of motivation higher. We
believe this fact is the best fit for systemic interpretation of the
sport activity mechanisms. Motivational arousal, produced by needs,
represents an essential component of afferent synthesis, and it is a
kind of filter external information coming into the CNS. If a level of
motivation
is high, that a process of afferent synthesis is more
effective. A process of afferent synthesis promotes to optimization of
acceptor result of action and to formation to executive program, that
finally, causes decrease the "the physiological price".
It's shown, that each stage result had physiological price. If
a power of physical activity stepwise was increased, "the physiological
price" stage result (%HR) significantly increased (p<0.05). There is a
positive correlation between the values of stage result and it's
physiological price (%HR) (r=0,987, p<005).
Index Robinson (DP) is positively correlated with the value of the
maximal oxygen consumption, which allows us to considering it as an
indicator of the level of sportsman physical efficiency. It is
revealed, that the physiological price of stage results and
indicator DP grow with increasing of load capacity of a stage; however,
the degree of the involvement of cardiac and vascular components to
different systemoquant's stages is various. It's shown, that a separate
systemoquant's
stages
has the various system organization of
functions.
Thus, when the intensity of physical activity is increasing,
then the system organization of functions is changing
and the
"
physiological price" of stage results grows, however it processes are
modulating by sportman's motivation.

71




..
-
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a.kolpakov@nphys.ru

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-

INTERACTION BETWEEN PERIPHERAL AND CENTRAL PARTS OF THE


ENDOGENOUS OPIOID SYSTEM UNDER EMOTIONAL STRESS
Kolpakov A.A.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
a.kolpakov@nphys.ru
The aim of this work was to study the interaction between
peripheral and central divisions of the endogenous opioid system when
exposed to stressors. The influence of peripheral ligands of mu-opioid
receptors, not entering BBB, on emotionality, as well as on the
72

activity of the central endogenous opioid system were studied. Level of


anxiety was tested over elevated plus maze. Beta-endorphin secretion
were present by in vivo microdialysis followed by the immunoenzyme
analysis. Density and affinity for opioid receptors in different parts
of the brain have defined by radioligand method. It was found that
peripheral mu-opioid receptor agonist loperamide has anxiolytic
effects. Loperamide reduces, and metilnaloxone reliably increases the
emission of beta-endorphin in intercellular space rat cingulate cortex,
as well as the density and affinity for opioid receptors in the brain
cortex and midbrain. Emotional stress leads to a small increase in the
level
of
beta-endorphin
in
the
cingulate
cortex.
Peripheral
introduction
of
loperamide
significantly
enhances
release
of
neuropeptide under stress. It is shown that in the vagotomized rats
loperamide, entered intragastricaly has no effect on rats anxiety. The
obtained data indicate that effects on peripheral opioid receptors can
lead to an opposite effect in the central nervous system by altering
the activity of the endogenous opioid system and the resulting change
in sensitivity to stress. These effects appear to be tranfered ti CNS
through the vagal afferentation.


-

..1, .. 2, .. 1, .. 2,
.. 1, .. 2, .. 2,
.. 2, .. 1
1

, ,
- , ,
konorova.irina@yandex.ru

().

(),

,
[ .. ., 1998; .. ., 2009].
toll-like TLR9,
.
()
[ ., 2000]. ,
() [ .. .,
2009].

-
.
. (n=25)
I- (n=12) II- (n=7) (
73

-, 1999), ,
;
1 ;

(Re=8000). (HUVEC)
NO

CuFL.
.
196[117;240], 0,42[0,32;0,56] / .
(r= 0,54, p<0,024).
,
, , , (r=
0,96, p<0,001) (r= 0,64, p<0,001)
. I-
,
, , 1
(p<0,01 ). II-
(p<0,05 p<0,01 ).
, 1 .
(r= 0,92,
p=0,027 r= 0,88, p=0,048 ) 1
(r= 0,90, p=0,037).
1-5 /
4 NO
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1,3 28 .
NO
( k= 0,98, p<0,0001).
. ,

, ,
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.

CpG-

NO-
, NO
.

74

CIRCULATING CELL-FREE DNA IN MECHANISMS OF REGULATION OF


CARDIOVASCULAR SYSTEM IN NORM AND ITS DISREGULATION IN
ARTERIAL HYPERTENSION
Konorova I.L. 1, Kostuk S.V. 2, Amintaeva A.G. 1, Alekseeva A.U. 2,
G.V. 1, Ershova E.S. 2, Konkova M.S. 2, Veiko N.N. 2, Varakin Iu.Ia.
1

Research Center of Neurology, Russian Academy of Medical Sciences,


Moscow, Russia
2
Research Centre for Medical Genetics, Russian Acad. of Medical
Sciences,Moscow, Russia
konorova.irina@yandex.ru

Intensity of the organs blood supply is in inverse relationship


from the hydrodynamic blood flow resistance (HBFR). Cell-free DNA
circulating in blood plasma (pDNA), in norm mainly in the form of highmolecular fragments, reduces HBFR via improving blood fluidity
[Gannushkina I.V. et al., 1998; Konorova I.L. et al., 2009]. Fragments
of pDNA contain ligands for "toll-like" receptor TLR9 which expresses
on endothelial cells. High-molecular transcribed region of ribosomal
repeat (rDNA) is one of such fragments [Veyko N.N. et al., 2000]. We
have shown that rDNA collects in pull of pDNA in patients with arterial
hypertension (AH) [Konorova I.L. et al., 2009].
The aim of this study was to estimate a contribution of pDNA
fragments to regulation of cardiovascular system activity in norm and
its disregulation in arterial hypertension.
Technique. Blood samples from healthy donors (n=25) and patients
with essential AH of the 1st (n=12) and the 2nd (n=7) degree (1999 WHOISH guidelines for the management of hypertension) not complicated by
atherosclerosis were used in the study. We evaluated: concentration of
pDNA by a fluorimetry method, concentration of rDNA in plasma and its
maintenance in 1 ng of pDNA by a quantitative non-radioactive
hybridization, HBFR of the blood samples by the time of their course
through a glass capillary in standard turbulent flow conditions
(Re=8000). NO quantity in a culture of human umbilical vein
endothelial cells (HUVEC) was estimated after adding pDNA of the donors
or the patients into a medium of cultivation by means of fluorescent
microscopy and spektrofluorimetry using fluorescent CuFL dye.
Results. Concentration of pDNA of healthy donors was 196[117;
240], and of rDNA was 0,42[0,32; 0,56] ng/ml of plasmas. The inverse
relationship of HBFR from concentration of pDNA (r = 0,54, p=0,024) is
revealed. Decrease in HBFR is noted both at reduction and at increase
in pDNA concentration concerning a median that was combined,
respectively, with increase (r = 0,96, p<0,001) or reduction (r =
0,64, p<0,001) the maintenance of rDNA in pull of pDNA without change
of rDNA concentration in plasma. In patients with AH of the 1st degree
pDNA concentration and HBFR were lowered but didn't differ from norm,
however the rDNA level both in plasma and in 1 ng of pDNA was elevated
(p<0,01 for both cases). In patients with AH of the 2nd degree
concentration of pDNA and HBFR were raised (p<0,05 and p<0,01
respectively). Thus the rDNA level both in plasma and in 1 ng of pDNA
75

didn't differ from norm. Inverse relationship of HBFR and average


arterial blood pressure of patients from concentration of rDNA (r =
0,92, p=0,027 and r = 0,88, p=0,048 respectively) and its contents in
1 ng of pDNA (r = 0,90, p=0,037) is revealed.Addition of the control
donors pDNA (1-5 ng/ml) into the HUVEC culture stimulated an increase
by 4 times of NO concentration both in cells and in the extracellular
environment, but of the patients pDNA, on the contrary, reduced it by
1,3 28 times. The inverse exponential relationship between the
maintenance of rDNA as a part of pDNA and concentration of NO in the
HUVEC culture (coefficient of linear regression k = 0,98, p<0,0001)
is revealed.
Conclusion. In norm, an emergence of DNA in a form of highmolecular fragments in blood circulation promotes improvement of organ
blood supply, on the one hand, through improvement of blood fluidity,
on another one, through activation of endothelial receptors and blood
vessel dilation via production of NO. Disturbance of base sequence
balance in a pull of circulating pDNA specifically in the form of
increase in the content of genome CpG-rich repeats leads to suppression
of NO synthesizing function of endothelium at an early stage of AH
that promotes deficiency of NO and can serve as a reason of
endothelial dysfunction development.


.. 1, ..

1,2,3

, ..

1,2,3

, ,
- , ,
3
-
.. , ,
kopaeva_my@nrcki.ru
2


,
. , , ,
.


. 5--2-
()
,
, , .

76



,

.

- C57l/6,
2-3 ,
20-30 . 100 /
0,1 10
1 . 6
,
. 6
: 3 , 3
1 1 ,
2 , 1 . +
, 3--3-
() 20 / 1 ,
, ,
. 2 72
,
. Leica VT1200S

50


.
Olympus FV10i Bitplane Imaris
7.4.2.
,
Lateral 0.48-3.00 +
.
,
2 .
( ),
. ,
, 72 .
2 72 ,
,
.
.
,
.

11.G34.31.007.

77

DNA SYNTHESIS IN MOUSE MOTOR CORTEX AFTER CONTEXTUAL


FEAR CONDITIONING
M.Y. Kopaeva1, O.I. Efimova1,2,3, K.V. Anokhin1,2,3
1

NRC Kurchatov Institute, Moscow, Russia


Moscow Institute of Physics and Technology, Moscow, Russia
3
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
kopaeva_my@nrcki.ru
2

Molecular mechanisms of long-term memory formation require


synthesis of proteins and RNAs. It was shown, that DNA synthesis is
also involved in memory mechanisms. Injection of DNA synthesis
inhibitors in time intervals around training evoked amnesia. Inhibition
of neurogenesis in adult hippocampal dentate gyrus impairs long-term
memory. Incorporation of nucleoside analogs during learning have been
demonstrated not only in classical neurogenic zones, but also in
neocortex of rats, rabbits and monkeys. We aimed to investigate
learning-induced nucleoside analog 5-bromo-2'-deoxyuridine (BrdU)
incorporation in adult mouse brain: to calculate number of BrdUpositive cells in hippocampal dentate gyrus and motor neocortex in
control and fear conditioned mice 2 h and 3 days after training and
possible involvement of reverse transcription mechanisms in this
process.
We used C57l/6 male 2-3 month old mice weighting 20-30 g. Animals
were divided on 3 experimental groups. Mice were intraperitoneally
injected with BrdU (100 mg/kg in 0,1 ml/10 g of body weight) 1 h before
training. Active control group was placed for 6 min into experimental
camera where they freely explored a new environment, without foot shock
delivering. Fear conditioning group was placed for 6 min into
experimental camera where 3 min they freely explored a new environment,
then 3 foot shocks (1 mA, 2 s) were delivered with 1 min interval
followed by 1 min again for exploration. Mice from Fear conditioning +
AZT group received injection of reversed transcriptase inhibitor, 3azido-3-deoxytymidin (AZT) (20 mg/kg in 0,1 ml/10 g of body weight) 1
h before training, right after BrdU injection. 2 or 72 h after training
one part of animals was tested for long-term memory and other was
anesthetized and after transcardial perfusion brains were removed for
further analysis.
Parasagittal sections 50 mkm were cut on
Leica
VT1200S vibratome and fluorescent immunohistochemical reaction on
floating sections was performed. Stained sections were imaged on
confocal microscope system Olympus FV10i and analyzed with Bitplane
Imaris 7.4.2 software. BrdU+ cells were counted on every sixth section
in hippocampal dentate gyrus, primary and secondary motor cortex
(Lateral 0.48-3.00 mm), then general quantity of BrdU+ cells per brain
structure was calculated.
Fear conditioning stimulated DNA synthesis in adult mouse brain
detected already 2 h after training.
DNA synthesis increase was
prominent both in classical neurogenic zone (hippocampal dentate gyrus)
and in motor neocortex. Number of BrdU-positive cells did not decrease
72 h after training. Contextual test 2 and 72 h after training revealed
78

long-term, but not short-term memory impairment in AZT injected group.


AZT injection before training produced significant decrease of BrdU
incorporation in motor neocortex detected 72 h after fear condition.
Thus, our results demonstrated learning-induced DNA synthesis in adult
mouse brain.
Supported by Russian Government grant # 11.G34.31.0071.




.., ..
-
.. , ,
e.koplik@mail.ru
, ()
- ,
. ,

- (),
.
- [Chen
G., Castro W. et al. 1997].

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40 - 40
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( .. 2002)
- 24

( .. 1986)..

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79

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(<0.05)..


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.

MORFOFUNKTIONAL CHANGES OF THYMUS IN RATS WITH DIFFERENT


TYPE OF BEHAVIOR DURING EXPERIMENTAL HEMORRHAGIC STROKE
Koplik E.V., Ivannikova N.O.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
e.koplik@mail.ru
It is known, that the stress - realizing system of organism
borrows a particular role in development of hemorrhagic stroke. It was
proved, that the hemato-encephalic barrier damages in condition of
hemorrhagic stroke, therefore proteins of brain come into blood
vessels. The -cell link of immunity was involved in the immune answer
when nervous tissue was damaged [Chen G., Castro W. et al. 1997].
Animals
with
different
prognostic
stress
resistance
were
characterized by different degree of thymus in condition of emotional
stress [K.V. Sudakov 1990].
The work was designed to compare the changes in thymus structure
in 40 high-active
and
40 low-active (in behaviour in the open
field test) Wistar rats
under control condition and during
intracerebral hemorrhage period.
Recently, it has been shown that
80

individuals in a rat population differ in their sensitivity to


loading with a similar type of stress. Rats that show greater
locomotor's activity and agility in the open field
test are more
resistant to acute stress exposure in comparison with less active
rats (Koplik E.V. 2002). Stressed rats (active and passive specimens)
were exposed to emotional stress. We used the model of aggressive-andconflict behavior, which was induced by tail fixation for 24 h (Yumatov
.., 1986).
The research of the thymus weighting coefficients had shown, that
the hemorrhagic stroke was a stress effect, and stress-resistant
animals had a small change of weight coefficients of a thymus, in
contrast of the stress predisposed rats. The analysis of the thymus
weighting coefficients in rats, who had stressed before experimental
hemorrhagic stroke, had shown that the weight of thymus of the stressresistant animals was reduced. It was watched, that in stress
predisposed to emotional stress rats had significantly changes of
weighting coefficients and thymus during 7 day of experiment.
On the 1, 3 and 7 day after the operation had shown, that the
thymus micro architectonics of the stress predisposed rats reacted by
more expressed changes, than the stress-resistant animals. It was
shown, that stress - resistant and time of hemorrhage ( < 0.05)
affected on changes of square both cortex, and cerebral substance of
the thymus. The density of cell elements on a unit area of thymus,
cerebral from microscopic section was significant decreased in
comparing with control groups animal, whereas cortex substance was
increased. The study of dynamic changes of the contents of cell
elements in cerebral, cortex substance and sub capsular zone had shown
the significant decreased of small lymphocytes number( it was
significant decreased in a sub capsular zone and cortex substance in
stress predisposed animals in 72 hours).
The results of this study allowed us to formulate an idea, both
stereotypic and autoimmune mechanisms are involved into intracerebral
hemorrhage progress.


-

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1

-
.. , ,
2
. .. , , .
e.koplik@mail.ru

Jolli J. (1953)
-
.
81

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,
( .., .., 1996).

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108

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( .., 2002).


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, 3-
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,
21% 19% (),
22%.
- ,
,

31% 30% (),
32% 26%, (),
30% 21%
().
7-
. 14-



.

82

THE STRESS EFFECTS ON LYMPH-EPITHELIAL STRUCTURE SMALL


INTESTINE OF RATS WITH DIFFERENT STRESS-RESISTANT
Koplik .1,
1

Ivanova ..2

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


2
I.M. Setchenov The first MSMU, Moscow, Russia
e.koplik@mail.ru

In 1953 Jolli J. Regarded presence of lymphocytes among cages


epithelial as limfo-epitelial symbiosis and has specified in presence
positive tropism lymphocytes to epithelial to a cover. Epithelial it is
considered as an element of the microenvironment integrated in lymphoid
a fabric which is shipped directly in a mucous membrane (Sapin M. R,
Etingen L.E., 1996).
The aim of this study was to determine the characteristics of the
reaction lympho-epithelial structures of the small intestine of rats
with different stress tolerance when exposed to acute emotional stress.
Experiments were performed on 108 high-active
and
low-active (in
behavior in the open field test) Wistar rats. (Koplik E.V., 2002).
Acute stress was modelled by immobilizing the animals and
applying electrocutaneous stimulation a 1-h stochastic regime. Directed
by experiment were guided by requirements of the World society of
protection of animals (WSPA) and the European convention on protection
of experimental animals. After head removals from an animal took away
lean and ileum a gut. Manufacturing of histologic preparations has been
spent by a well-known technique with coloring hematoxilin and eosin.
After hour stressful influence, and also in 1, 3rd and 7 days in a
mucous membrane at a small intestine are revealed the expanded and
devastated blood vessels (vascular stasis), plasma of blood and
individual erythrocyte in intercellular space. The Greatest quantity of
destructively changed cages and macrophages at stress-steady and
stress-predisposed of rats is revealed in 3rd days after unitary
stressful loading. Against vascular reaction in 3rd days after the
termination of sharp emotional stress at stress-steady and stresspredisposed of animals in apex parts of fibers at lean and ileum guts
observed destruction epithelium and a devastation storms fibers. Often
at stress-predisposed of individuals the given changes "joined" mass
destruction cages lymphoid a number in apex parts of fibers.
Morphometric researches have shown that in 3rd days after
stressful influence at stress-steady of rats, in comparison with
control individuals of the group, decrease in height of fibers at a
lean gut and ileum guts on 21 % and 19 %, accordingly, the areas
epithelium at a lean gut in on 22 % is revealed. In similar terms of
experiment at stress-predisposed of rats, in comparison with control
individuals of the group, area decrease lymphoid fabrics at a lean gut
and ileum guts on 31 % and 30 %, accordingly, heights of fibers at a
lean gut and ileum guts on 32 % and 26 %, accordingly, the areas
epithelium at a lean gut and ileum guts on 30 % and 21, accordingly is
revealed.

83

Similar changes at stress rats were observed till 7th days after
stressful influence. Through 14 days after the termination of stressful
influence the cellular structure lymphoid formations in fibers at
mesenteric to a part of a small intestine and morphometric researches
the areas epithelium a mucous membrane of the given bodies corresponded
to control indicators.

..
-
.. , ,
i_korobeinikova@mail.ru



. ,

.

,
(vigilance) (expectancy),

.
,

.
,

.
-1 -2
,
, . 1
, -1 (7-10 )
70 % . 2-
(9 ) ,
-2 (10-13 ) 70%
., ,


), 1 2-,

. 2-

84


.
, 1- .

,
,

.

SUCCESS OF THE TEST TASK PERFORMANCE BY STUDENTS WITH


DIFFERENT SPECTRAL -RHYTHM CHARACTERISTICS IN THE BASELINE
ELECTROENCEPHALOGRAM
Korobeinikova I.I.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
i_korobeinikova@mail.ru
Studies of the EEG a band parameters as indicators of cognitive
and other types of human activity have aroused great interest recently.
Convincing evidence that changes in different -activity frequency
bands are correlates of different cognitive functions have been
obtained. Desynchronization in the low and middle bands is associated
with the processes of attention, such as vigilance and expectancy,
while desynchronization in upper bands reflects an increase in mental
activity. In the studies in which the analysis of changes in different
-activity
frequency band was made in connection with the
effectiveness of different types of purpose-oriented human activity,
baselaine characteristics of the -rhythm subbands were taken into
account, while the EEG -rhythm parameters in the state of relative
rest are characterized by great individual variance. Therefore, the aim
of this investigation was to study the relationship between the
individual features of the human encephalogram -rhythm in the state
of relative rest and the parameters of successful purpose-oriented
activity with the elements of memorizing and prediction.
The subjects were divided into two groups according to the -1
and -2
spectral powers in the occipital derivations of the EEG
recorded in the initial state with their eyes closed. Group I included
subjects whose -1 rhythm spectral power (7-10 Hz) was more than 70% of
the total -rhythm band power. Group II included subjects whose -2
rhythm spectral power (10-13 Hz) was more than 70% of the total rhythm band power. It was established that, in the tasks requiring
prediction of the subsequent result (memorizing a certain sequence of
signals and its subsequent reproduction on the monitor screen), group I
subjects differed from group II subjects in fewer sequence errors and a
greater number of accurate predictions. In group II subjects, a
decrease in the 9-band spectral power in the EEG of the central and
frontal cortical areas was observed compared to the baseline.
Therefore, the EEG -rhythm power at the memorizing stage was lower in
them than in group II subjects. The results suggest that the baseline
85

characteristics of -activity can be regarded as prognostic criteria of


similar types of activity.



..1, ..1,2
1

-
.. , ,
2
..
, ,
a.kravtsov@mail.ru

,
, , , ,
.



.
,
()
(), (), (), ()
.
,
, ,
.

20
.
.

.

86

DYNAMICS OF NEUROTRANSMITTER PROCESSES IN THE DORSAL


HIPPOCAMPUS OF RATS DURING EMOTIONAL STRESS
Kravtsov A.N.1, Umryukhin A.E.1,2
1

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


I.M. Sechenov First Moscow State Medical University, Moscow, Russia
a.kravtsov@mail.ru

Stress exposure is known to produce an individual effect on the


molecular, neurotransmitter, immune, homeostatic, and behavioral
components of various functional systems in the body. However, the
mechanisms of emotional stress and resistance to stressogenic factors
are poorly understood.
This work was designed to evaluate (by means of microdialysis) the
content of key neurotransmitters in the dorsal hippocampus of Wistar
rats during and after immobilization stress.
We revealed that the animals exhibiting an active and passive
pattern of behavior in the open-field test are characterized by the
specific qualitative and quantitative dynamics of norepinephrine (NE),
dopamine (DA), glutamate (Glu), and -aminobutyric acid (GABA) in the
dorsal hippocampus. During stress exposure and post-stress period the
amount of DA increased in behaviorally active rats, but decreased in
passive animals. NE content was shown to be elevated in active
specimens, but remained unchanged in passive rats. The level of Glu in
active rats decreased by the end of a 1-hour post-stress period. By
contrast, Glu concentration in passive animals was elevated over the
first 20 min of stress exposure and poststress period. The amount of
GABA increased in active rats during stress exposure, but decreased in
passive animals.
Our results indicate that stress has a complex effect on the
central
mechanisms,
which
underlie
the
relationship
between
neurotransmitter processes in the dorsal hippocampus of rats with
various behavioral characteristics.

87


HLDF-6 (TGENHR)

..1, .. 1, ..2, .. 2,
.. 2, ..3, .. 3, ..4,
..5, .. 1, .. 1
1

. ..
.. ,
. ,
2
.
.. .. , . ,
.,
3
-
.. , ,
4
, .
,
5
- . ..
, . ,
vmlipkin@mx.ibch.ru
HL-60

HLDF
(Human
Leukemia
Differentiation Factor) (54 ..),
HLDF-6
(TGENHR),

. HLDF-6

HLDF-6
, ,

.
HLDF-6

, -,
, , .
,
HLDF-6
3-30 /
.
(
) , 1-50
/

.
HLDF-6.
SPF-
()
(. , 2005). ,
, HLDF-6
2000 / ,
4 .
HLDF-6 2213747.
88

,
HLDF-6

( ,
).


14.N08.11.0002.

DEVELOPMENT OF A NOVEL PHARMACEUTICAL ON THE BASIS OF HLDF-6


(TGENHR) PEPTIDE FOR PROPHYLAXES AND TREATMENT OF
NEURODEGENERATIVE AND CEREBROVASCULAR DISEASES
Lipkin V.M.1, Bogachuk A.P. 1, Murashev A.N.2, Rzhevsky D.I. 2, Azev V.I.
2
, Storozheva Z.I.3, Sherstnev V.V. 3, Zolotarev Yu.A.4, Kovalev G.I.5,
Surina E.A.1, Smirnova E.V.1
1

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian


Academy of Sciences, Moscow, Russia
2
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
of the Russian Academy of Sciences, Pushchino, Moscow region, Russia
3
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
4
Institute of Molecular Genetics of the Russian Academy of Sciences,
Moscow, Russia
5
Zakusov Institute of Pharmacology of the Russian Academy of Medical
Sciences, Moscow, Russia
vmlipkin@mx.ibch.ru

Earlier, a new differentiation factor HLDF (Human Leukemia


Differentiation Factor) was isolated from the HL-60 cells. HLDF is
relatively small protein (54 a.r.), in the sequence of which a sixmembered HLDF-6 (TGENHR) peptide was identified, completely reproducing
differentiating activity of a full-sized factor. HLDF-6 peptide
possesses nootropic and neuroprotective activities. The direct
evidences have been obtained of neuroprotective effect of HLDF-6 on the
primary culture of neuronal cells of hippocampus, cerebellum and
immunocompetent cells. The HLDF-6 expresses anti apoptotic activity,
defending the cells from the beta-amyloid, sodium azide, ethanol
activity, and also from cold shock and hypoxia. The tests performed on
various species of animals have showed that, in the intact animals,
upon central and system administration of HLDF-6 in the doses 3-30
mcg/kg improvement was observed of forming and maintenance of long-term
memory. The peptide is active not only on the models of associated
learning, but also on the non-associated one.
On the experimental models of clinical pathology Alzheimers
disease and ischemic stroke the peptide in the doses 1-50 mcg/kg was
shown to withdraw the pronounced cognitive deficit and to promote the
recovery of disturbed memory.
We have begun the pre-clinical trials of HLDF-6 peptide. The
investigations are performed on laboratory SPF- animals in compliance
89

with the requirements of the Guide on experimental (pre-clinical) study


of new pharmacological substances. (M., Medicine, 2005). According to
the results obtained during acute toxicity study, the HLDF-6 peptide in
the dose 2000 mg/kg does not display any toxic effects that satisfy the
requirements of the lowest the 4-th hazard category low-hazard
substances
We have Russian patent 2213747 for the HLDF-6 peptide.
Thus, the results obtained permit to consider the HLDF-6 peptide
as a perspective compound for creation a novel pharmaceutical for
prophylaxes and treatment of neurodegenerative and cerebrovascular
diseases (Alzheimers disease and ischemic stroke).
The work is supported by the Molecular and cellular biology RAS
Presidium
Program
of
basic
research
and
State
contract

14.N08.11.0002.


..
..
, ,
llm555@yandex.ru
,
,
, , ,
, , , ,

, , .
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.
( ..,1997, 2003, 2011),
, ,
, -
,
.
,
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90

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. ,

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(
..,
2012),

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.

THE CENTRES OF DIGESTION AND ORGASM


Litvinenko L.M.
I.M.Setchenov First Moscow State Medical University, Moscow, Russia
llm555@yandex.ru
Attributes of orgasm at the person as the pleasure accompanying by
the involuntary contraction of mimic muscles, deforming the face,
involuntary contraction of the chewing muscles accompanying the
gnashing of teeth, changes of the breath, pulse, occurrence of low
sounds, groans, involuntary contractions of perineal muscles and
internal organs of the pelvis, and also muscles of the extremities,
especially lower extremities and others are known. Why it occurs? In
the literature there is no answer to this question. However all is
easier, than seems. All set forth above is precisely are stacked in
system of the work
of the digestion centers (Litvinenko L.M., 1997,
91

2003, 2011)
which are: the oral center of digestion consists of
nuclei of the facial nerve, pharyngeal center consists of nuclei of the
glossopharyngeal nerve, the gastroenteric center consists of nuclei of
the vagal nerve, evacuation center of digestion nuclei of pelvic
nerves and pudendal nerve. The oral center of digestion through the
facial nerve innervates the mimetic muscles, create conditions for work
of the olfactory, visual, gustatory analyzers, Jacobsons body. The
glossopharyngeal nerve ensures the work of the acoustic analyzer, the
chewing apparatus (chewing muscles, dentoalveolar system ) and the
certain level of the blood pressure in the head, innervations of the
stylopharyngeus (mechanism of swallowing) and of the tonsils (the
organs of immune system). The vagus nerve provides innervations of the
muscles of the palatum molle, of the pharyngx, laryngx, esophagus,
heart, lungs, the liver, pancreas, a stomach and the small intestine
and the right half of the large intestine, testis and ovary. The
splanchnic pelvic nerves innervate the left half of large intestine,
the organs of the small pelvis, including urogenital organs; they work
in coordination with sacral plexus which innervates the perineum and
lower limbs. All these centers have representatives in diencephalon,
basal nuclei and in the cortex of the brain, in which centers of
digestion, breath, blood circulation, sexual, the centers of pleasure
and aggression, the emotional centers, memories and thinking centers
are situated together It is noticed, that from the organs of the head
to pelvis located near the organs, carrying out the digestive, immune,
indicating histocompatibility, and sexual functions. It is connected by
that the organs of digestive and sexual systems are single whole, they
concern to the trophy
system, (Litvinenko L.M., 2012), which
are
formed in the embryogenesis before all organs and systems at the stage
of 2 germinal layers, on 12-th days of human development. Digestive
system provides nutrition every second, every minute, constantly,
within days and months, years with deposition of necessary substances.
The genital system provides the deferment nutrition for other animals
(the food biological chain) and for the organism during the critical
situation (it may be cannibalism). These systems have various incentive
mechanisms. The strongest is orgasm for creation of the food biological
chain. All this is fixed genetically. In the classic orgasm we observe
irritation of the centers of the digestion from the top downward, what
are accompanied with involuntary contractions of muscles and the other
effects connected with analyzers and organs, which are under the
influence of the centers of digestion. The orgasm is individual the
wave through the centers can go also from below upwards, from middle downwards or upwards. It is known that people with remote genitals are
experience orgasm. The moment of the upbringing has enormous value that
is reflected in paints of orgasm. Various pathological variants of the
senses of the orgasm were fixed,
a lot of them, they are described in
the scientific and criminal literature. Some of them can be treated.
However, the sexual maniacs and the pedophiles are useless to treat by
means of the chemical and physical castration. The treatment of these
people should be at the genetic level (suppression of genes necessary).
The most important aspect is the proper upbringing of children man with
the consideration of genetic norm and anomalies.
92


.
.., .., .., ..




,

.
(..)


() ,

,
() (CV) R-R
. ,
(138/84)
(122/80) , CV
, (2,8%16)
(4,3%0,19) .
CV .
( CV)
( )

,
, ,
, ,
.
,
,
.
,
,

(>15%)
,
.
D

-

,

.
.
( .)
,
, ,
,
;

, .
.
93

(..)

.
,
- ,
,

THE SYSTEMO-QUANTUM ANALYSIS OF RHYTHMICAL COMPONENTS OF AP


ON THE BASIS OF"PASSING ISCHEMIA"
OF MYOCARDIUM OF AIR TRAFFIC CONTROLLERS.
Mammadov A.M.,

Aliyev A.Kh., Khudaverdiyev A.S., Panahova G.I.

Azerbaijan Medical University


National Aviation Academy of Azerbaijan
Research of earlier manifestation of various cardiovascular
disturbances belongs to number of actual problems of a human factor in
aviation, in the course of professional activity of aviadispatchers.
Systemo-quantum
(K.V.Sudakov)
research
of
psychophysiological
indicators of dispatchers of the air traffic control (ATC) in various
conditions of day and night changes, in the course of real professional
activity, revealed in "almost healthy" groups at the beginning of
change, generally rhythmical components in changes of the arterial
pressure (AP) and variability (CV) of R-R intervals of a cardiac
rhythm. In the course of direct activity, the arterial pressure raised
on the average to (138/84) and decreased almost to norm (122/80) in
pauses and after work, while changes of CV had an opposite tendency,
decreasing (2,8%16) during activity and raising (4,3%0,19) in
pauses. In such "rhythmic" nature of changes the AP and CV is put
important adaptive sense.
However "rhythm" of changes of the specified indicators (the AP
and CV) were disturbed (at the expense of not complete recovery of
their values in pauses) in the course of intense professional activity
of dispatchers, especially in "groups of risk" and in night shifts, in
conditions when a circadian rhythm of the functional systems supporting
the arterial pressure, is maximally disturbed.
It is important to note that disturbances of rhythmical components
of AP during activity and pauses, precede increase of its values and
there can be a peculiar warning signal of expected increase of arterial
pressure.
Researches also showed that in this period these changes are
accompanied, also by increase of dispersive indexes (15%) lowamplitude fluctuations of the electrocardiograms revealing development
of early of a "passing" form of ischemic disturbances of a myocardium.
Long-term maintenance of such emotional-intense conditions with
disturbed rhythmical components leads to increase and stabilization of
94

AP values and indicators of "passing ischemia" of myocardium that is a


pathogenetic basis of formation of various pathological shifts in
cardiovascular system of an organism of air dispatchers. However these
changes easily removes by non medicinal correctional influences.
Use of a method of a relaxation (on K.Gekhta) allows not only to
restore the disturbed rhythm, to normalize value size the arterial
pressure and other psychophysiological indicators, but also in advance,
"a curve relaxation" to determine ability to a relaxation by decrement
of attenuation, to predict extent of disturbance of rhythm and values
of the AP; according to "systemo-quantum" of the forthcoming
professional activity, individually for each dispatcher of the air
traffc control. This technique can be applied for professional
selection and career guidance.
Thus, "systemo-quantum approach" (K.V.Sudakov) to researches
allows
to
define
the
rhythmic
organization
of
analyzed
psychophysiological processes. Disturbances of rhythmic components of
arterial pressure changes, as one of the main signs of formation of
cardiovascular diseases, is a primary signal of expected increase of AP
that gives the chance to hold preventive correctional measurements for
normalization of a rhythm in time and warning about the increase of
arterial pressure of dispatchers at air traffic control.


,
.
.., ..
-
.. , ,
l.v.mezentseva@mail.ru
, ,
,
.
.
, ,

, ,

.

, ;
,
,



.
95

MOD2K,
CHAOS ver. 3.0., Windows XP.
PP, PQ RR
.
3-
: , 1- 2-
, .
(F1)


. (F2)
.
(F3)
.
,

,

-
;


(, 1- 2- );

ANALYSIS OF CHANGES IN HEART RATE VARIABILITY DURING


FAST EXTRACARDIAL IMPULSATION IN THE SINOATRIAL NODE
Mezentseva L.V., Pertsov S.S.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
l.v.mezentseva@mail.ru
It is known that fast extracardial impulsation in the sinoatrial
node modifies the degree of heart rare variability. The present study
presents theoretical and experimental investigation of this effect.
Theoretical investigation is based on the mathematical modeling of
impulse conduction in the cardiac conduction system. The experimental
investigation in acute experiments on dogs revealed quantitative
correlations between the frequency of extracardial impulsation in the
sinoatrial node and changes of heart rate variability. The experiments
revealed increase in the delay of atrioventricular conduction during
fast extracardial impulsation in the sinoatrial node; the transitions
between different regimes of heart rate dynamics; Wenkebach's
periodicity.
The
obtained
quantitative
characteristics
of
atrioventricular conduction are used for checking the proposed
mathematical model of disturbances of the ventricles rhythm on fast
96

electric activity of the atria.


The mathematical model is based on the known principles of
experimental electrophysiology of the heart, describing the propagation
of electric excitation in its different structures. The model is
realized in the form of computer program MOD2K entering the author
program complex CHAOS ver.3.0, working in Windows XP. The program
permits calculating time series PP, PQ and RR intervals at different
values of the input extracardial impulsation frequency.
A
mathematical modeling revealed the following three regimes of heart
rate variability: linear dynamics, the 1st degree chaos, and the 2nd
degree chaos and two critical points defining transitions between these
regimes. The first critical point (F1cr) defines transition of cardio
dynamics from linear to nonlinear regime and adaptive reaction on
stressor and other external extremal influences. The second critical
point (F2cr) defines physiological boundary between norm and pathology.
The third critical point (F3cr) defines boundary between life and
death.
Computer simulation shows that the mathematical model can account
for most principal properties of the heart rate disturbances during
fast extracardial impulsation in the sinoatrial node: increase in the
delay of atrioventricular conduction; the transitions between different
regimes of heart rate dynamics (linear dynamics, the 1st degree chaos,
and the 2nd degree chaos); Wenkebach's periodicity. The present model
provides a unified platform wherein various types of ventricular
disturbances at external extreme loads can be simulated.

.., ..

. .. ..
, , 17997, -7, . -, 16/10
anna.mikhailova@ibch.ru
(OpdB) ,
:
Trpypanosoma ruzi, T. brucei T. evansi,
Leishmania major L. amazonensis. , ,
,
Esherishia
coli,
Moraxella
lacunata,
Salmonella
enterica,
Mycobacterium tuberculosis M. leprae,
Treponema denticola.
( , ),
. OpdB
,

-,
,

97

().

. , ,
. OpdB

.
. ,

.

OpdB

Arg/Lys.

, , , ,
, I II, VIP-, P, ,
Arg8- Lys8-, ,
-28. OpdB

,
.
600 ,
,
(Arg Lys). II,
, , II, I .,
Arg/Lys,
OpdB.
Serratia
proteamaculans
(PSP), OpdB. OpdB
S. proteomaculans 94 E. coli BL-21 (DE3)
pOpdB. PSP OpdB
(Yersinia pestis),
(S. typhi) (S. enterica).
PSP
26- ,
.
OpdB 21-24
KRKR-, Lys7.
. PSP
: 1-22, 8-22 (

Arg22

Lys7,
), 1-21 8-21( - Arg
1-22 8-22).
PSP
.
(10-04-01381-).

98

OLIGOPEPTIDASE B PROTEASE INVOLVED IN PATOGENESIS


Mikhailova A.G., Rumsh L.D
M.M.Shemyakin and Yu.A.Ovchinnikov Institute of Bioorganic Chemistry
RAS, Miklukho-Maklaya St. 16/10, Moscow SP-7, 117997 Russia
e-mail: anna.mikhailova@ibch.ru
OpdB
is a trypsin-like serine proteinase found in ancient
unicellular eucaryotes, such as trypanosomes Trypanosoma cruzi, T.
brucei, and T. evansi and leishmaniae Leishmania major and L.
amazonensis. Genes encoding this enzyme are also found in Gram-negative
pathogenic bacteria such as Escherichia coli, Moraxella lacunata,
Salmonella enterica, mycobacteria Mycobacterium tuberculosis and M.
leprae, and spirochete Treponema denticola. Oligopeptidases B are
important virulence factors in trypanosomal infections such as Chagas
disease and African sleeping sickness. Parasitic OpdB catalyze abnormal
degradation of host peptide hormones such as atrial natriuretic factor,
thus being implicated in pathogenesis of different trypanosomiases and
leischmaniases. It should be emphasized that genes encoding this enzyme
are not found in mammals. Thus, OpdB of protozoan parasites may serve
as therapeutic targets in search for pharmaceuticals against these
dangerous infections. Prokaryotic homologs of this protein are far less
studied, but are also supposed to be important targets for
antimicrobial chemotherapy.
Natural peptides with a high content of basic residues are
efficiently hydrolyzed by OpdB after Arg/Lys residues. This was
demonstrated using peptide hormones such as atrial natriuretic factor,
ACTH, bradykinin, angiotensins I and II, VIP peptide, compound P,
neurotensin, reduced Arg8- and Lys8-vasopressins, glucagon, dynorphin A,
and somatostatin-28.
It seems possible that OpdB takes part in the degradation of
antimicrobial peptides excreted by plants, invertebrates, and mammals
in response to a bacterial infection. There are about 600 antimicrobial
peptides with high content of positively charged amino acid residues
(Arg and Lys) destroying cells of different microorganisms. They
include buforin II, thanatin, melittin, magainin II, tachyplesin I,
etc. containing sequences of two or more Arg/Lys residues, which making
them potential substrates of OpdB.
A novel trypsin-like protease (PSP) from the psychrotolerant Gramnegative microorganism Serratia proteamaculans was purified. The enzyme
was found to be the previously unknown OpdB. The S. proteamaculans 94
OpdB gene was sequenced and the producer strain Escherichia coli BL21(DE3) pOpdB was constructed. The most homologous to the PSP amino
acid sequence is that of OpdB (deduced from the gene sequence) from
Yersinia pestis (causative agent of plague), S. typhi and S. enterica.
To investigate the action of PSP on oligopeptides, we have
chosen the 26-membered peptide melittin, a biologically active peptide
from bee venom. Melittin contains several potential sites of hydrolysis
by OpdB: the sequence 21-24 of four positively charged amino acid
residues (-KRKR-), as well as the residue Lys7. Under the action of
99

PSP, the four products are formed successively: fragments 1-22, 8-22
(corresponded to the hydrolysis of melittin after residues Arg22 and
Lys7), 1-21 and 8-21 (the products of the cleavage of C-terminal Arg
residues from fragments 1-22 and 8-22). The hydrolysis of the
antimicrobial oligopeptide melittin by PSP is a model of possible
biological functions of this enzyme.
This work was supported by the Russian Foundation for Basic
Research (Project 10-04-01381-.



..
. ..
.. , . .,
murashev@bibch.ru
(GLP)
, , ,

,
, ,
, ,
.
GLP
,
,
.

,
,
.
: , ,
, . GLP, ,
.

GLP, -
, ,
.
GLP , -
, .
, ,
,
, .

100

- ,
.
.
,
,

.

,
GLP,
(),
, .
,
,
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.

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GLP

, , .
,
, GLP .
,
GLP.

THE SYSTEM APPROACH - A BASIC PRINCIPLE OF GOOD


LABORATORY PRACTICE
Murashev Arkadiy N.
Branch of the Shemyakin and Ovchinnikov Institute of Bioorganic
Chemistry
Pushchino, Moscow region, Russia
murashev@bibch.ru
Good Laboratory Practice (GLP) is a system concerned with the
organizational process and the conditions under which non-clinical
health and environmental safety studies are planned, performed,
monitored, recorded, archived and reported. Principles of GLP should be
applied to the testing of test items contained in pharmaceutical
products, pesticides, food additives, feed additives, cosmetic
products, veterinary drugs and industrial chemicals. Principles of GLP
are a methodological basis for non-clinical studies.
The system approach is one of methodological directions of
scientific knowledge, it is focused on creation of the optimum approach
in noegenesis for the guaranteed purpose to receive the most full and
complete representation about investigated objects. The system approach
101

is based on the following main principles: integrity, hierarchical


pattern, structuring, plurality and consistency. GLP as to system, the
given principles also are inherent.
Principle of the integrity, allowing to consider simultaneously
system as a unit and at the same time as a subsystem for higher levels,
it is reflected in definition of the test facility. According to GLP,
the test facility means the persons, premises and operational units
that are necessary for conducting the study. A higher level for the
test facilities is GLP the system of the state including legal base,
the state body of monitoring and actually test facilities. A
subordinate level for the test facility can be, for example, the
persons, which includes the test facility management, the Quality
Assurance Unit and Study Directors as the minimum.
Hierarchical pattern - presence of set of the elements located on
the basis of submission. Realization of this principle of the system
approach is well visible on an example of the persons. The test
facility management is the maximum a level, the Quality Assurance Unit
includes personnel, which is independent of study conduct and is
designed to assure test facility management of compliance with
principles GLP, the study plan and Standard Operating Procedures (SOP).
For each study the test facility management appoints the Study Director
who has the individual responsible for overall conduct of a study.
A structuring, allowing analyzing elements of system and their
interrelation
within
the
framework
of
concrete
organizational
structure. As a rule, process of functioning of system is caused not so
much by properties of its separate elements, how many properties of the
structure. The test facility should have the strict structurally
functional organization. Each division of the test facility has the
individual competence which in the sum and ensure the functioning into
the test facility as a whole. Other example of a structuring of GLP can
be conducting the documentation, there are four separate kinds of
documents: the study plan, SOPs, the row data and the report. Each of
these documents has own functional loading, and together represent
harmonious system of the documentation without which GLP cannot exist.
Thus, the system approach as a direction of methodology of
scientific knowledge can be considered a basic principle of GLP.

102



..1, ..1,2, ..2,
..1, ..1
1

-
.. , ,
2
, ,
murtazina@yandex.ru

,
.

25

-
, 2
. 14

: , 2. 2- 14 25-

(TSE-systems,
). 3 3
.
2 (45 ),
, .


.
,
. ,
,
,

,
,

,

. ,
,

,
.

103

BEHAVIOURAL AND BIOCHEMICAL ANALYSIS IN RATS


WHEN INCLUDED IN THEIR DIET EXTRACT PHYTOECDYSTEROIDS
Murtazina E.P.1, Sidorova Yu.S 1,2, Mazo V.K.2, Zhuravlev B.V.1,
Kudryavcev D.S 1
1

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


Institute of nutrition, Russian Acad. of Med. Sci., Moscow, Russia
murtazina@yandex.ru

Studies was made in male Wistar rats kept in individual boxes. The
experimental animals daily was given phytoecdysteroids extract of the
natural substance Serratula coronata L with adaptogenic activity for 25
days, calculated daily diet adding 2mg per kg of rat body weight. At
the 14 day in the first subgroup of the control and experimental
animals was measured by enzyme immunoassay kits biochemical hormonal
status of the animals in the blood plasma concentration of
corticosterone, -endorphin and prostaglandin E2. From the 14th to 25th
days in the 2nd subgroup of rats was carried out the analysis of motor
activity and rate of learning instrumental food operant ability in
complex experimental hardware and computer system (TSE-systems,
Germany). The protocol of the study included 3 hourly and 3 diurnal
experiments. The number of clicks on two pedals was detected every hour
in order to obtain food pellets (45 mg), also the horizontal and
vertical locomotor activity and oxygen consumption was measured. The
studies have shown that the hormone levels investigated in plasma of
control and experimental groups did not differ significantly. It is
shown that rats of the experimental group was significantly faster
trained instrumental food operant ability. It was detected that the
experimental animals as compared to controls consumed significantly
more oxygen, wherein the horizontal and vertical level of motor
activity were not different. Analysis of the correlation relationship
of metabolic, motor and operant performance in learning rats of control
and experimental groups showed that the oxygen consumption provides
control rats general locomotor activity, whereas oxygen consumption and
physical activity of experimental rats correlated with the instrumental
activity. Thus, the study suggests that the addition to the diet of
phytoecdysteroids extract helps the organism adapt to the new
conditions and speeds up the processes of training and memory in
animals, without altering the hormonal profile in rat plasma.

104

ROLE OF PRO-INFLAMMATORY S100 PROTEINS IN AMYLOID DISEASES.


Morozova-Roche Ludmilla A.
Department of Medical Biochemistry and Biophysics, Ume University,
Ume, Sweden.
ludmilla.morozova-roche@medchem.umu.se
Proteins of S100 family, such as S100A6, S100A8 and S100A, play
critical
role
in
numerous
cellular
processes
including
cell
proliferation, differentiation, motility and danger signaling by
interacting with and modulating activity of target proteins. They are
also implicated in the numerous disease pathologies and their
expression level is significantly increased in many types of cancer,
inflammatory, neurodegenerative and autoimmune diseases. The functional
diversity of S100 proteins is achieved via multiple assemblies into
native homo and hetero oligomeric complexes regulated by Ca2+ and Zn2+binding. By using biophysical and biochemical methods, we have
demonstrated that both in vitro and in vivo S100A6, S100A8 and S100A9
proteins can form also alternative, non-native amyloid self-assemblies
including amyloid oligomers and fibrils. We have found that S100A8 and
S100A9 are involved in amyloid deposits in such seemingly distant and
unrelated amyloid diseases as corpora amylacea in ageing and cancer
affected prostate and amyloid plaques in Alzheimers brain tissues,
while S100A6 contributes to amyloid development in amyotrophic lateral
sclerosis. What all these diseases have in common is concomitant
inflammation and elevated level of S100 proteins, which can serve as
prerequisite for their amyloid assembly. The amyloidogenicity of S100s
is regulated by Ca2+ and Zn2+-binding and effectively competes with the
formation of their native functional complexes. Apart from forming
amyloids themselves S100 protein can also modulate the amyloid assembly
of major amyloid denominators of corresponding diseases. Their high
intrinsic amyloid propensity may lead to their amyloid depositions in
other ailments, which still need to be examined, especially if these
diseases have an increased expression of S100s. The implications for
therapeutic treatment and diagnostics of the amyloid diseases are
discussed.

105


BALB/C C57BL/6
..1, ..2, ..1, ..1
1

- . ..
, ,
koz.mar9@yandex.ru;
2
, .,

ikozlovskiy@mail.ru

()
,
, .
,
()
,
BALB/c, , C57BL/6, ().

- (),
,
BALB/c C57BL/6
,
.
10 /,
/, [ .. ., 2007].
0,075 /, . ,
: 5 30
. ,
, (,
) , 3- , 3-
.
,

).

, ,
.

- BALB/c
C57BL/6:

,
.

BALB/c ,
, , ,
. ,

, ,
106

, H3 BALB/c.
, -,

,

,
,

,
-
,


.

FEATURES OF ANXIETY FORMATION AND PECULIARITIES OF ANXIOLYTIC


EFFECT AFTER NALOXONE ADMINISTRATION IN BALB/C AND C57BL/6
MICE
Nadorova A.V.1, Kozlovskiy I.I.2, Kolik L.G.1, Kozlovskaya M.M.1
1

Zakusov`s Institute of Pharmacology RAMS, Moscow


koz.mar9@yandex.ru;
2
Adaptive physical activity department, Moscow Educational University,
Moscow, Russia
ikozlovskiy@mail.ru
The role of endogenous opiate system in the development of
anxiolytic effects of pharmacological agents for treatment anxiety
disorders is examined not enough. Previously it was shown
that
pretreatment with naloxone induced reduction of functional activity of
opiate system accompanied by modulation of anti-stress effect of
anxiolytic drug Selank in BALB/c (anxious) and C57Bl/6
(nonanxious) mice.
The aim of the present work was to study the dependency of
anxiogenesis in the model of novel environment on the endogenous opiate
system activity, level of emotionality and benzodiazepine tranquillizer
effects after its co-administration with non-selective antagonist of
opiate receptors naloxone.
Acute blockade of opiate system by naloxone (10.0 mg/kg, i.p., 5
min) took place before and after phenazepam administration (0.075
mg/kg, i.p., in Tween - 80, 30 min) The behavior of inbred male mice
BALB/c and C57BL/6 was assessed in open field test. The main
parameters measured were the peripheral activity, the central activity,
the vertical activity. General locomotor activity (GLA) has been
calculated as a sum of the total activities during 3 min. The level of
specific [3H]- flunitrazepam binding to P1 + P2 membrane fraction of
brain tissue was studied (ex vivo) after opiate system blockade by
naloxone (10.0 mg/kg, i.p., 30 min before decapitation), to examine the
binding capacity of GABAA benzodiazepine reception.
In OF test naloxone increased GLA in BALB/c mice, and decreased in
C57BL/6 mice. Naloxone did not antagonized phenazepam effects in both
mice strains. Naloxone pretreatment enhanced phenazepam effects on GLA
107

in OF test in BALB/c mice (p=0.0015, U-test) and in C57BL/6 (p=0.0846,


U-test). It was shown, that naloxone increased benzodiazepine reception
in BALB/c mice (p=0.0063, U-test) and in C57BL/6 (p=0.0993, U-test). It
is proposed that enhancing of anxiolytic effects of phenazepam should
be explained by naloxone-induced increase in the binding capacity of
GABAA benzodiazepine reception.
The results obtained demonstrate the importance of functional
state of endogenous opiate system in anxiolytic effects of
benzodiazepine tranquillizers and give proof of further investigations
in order to reveal the role of opiate system in anxiolytic effects of
anti-anxiety drugs with different chemical structure.




.., .., .., .., ..,
..
-
.. , ,
v.nikitin@nphys.ru


. , ,
.

.

()
, ()
.

, .
3- ,
6-10 .
1,5 ,
.
, 2
NMDA -801
, ,
.
. -801
10 20
. 30 -801
,
. ,
30 , ,
,
108

10 20
30-
.
1- ,
30 .
1
, .
5- .
, 5

,

.

12 .
.
12
, 14
. (-)

. ,


,
,
.
,
,
.

-
, ,
. ,
, ,
, , ,
,
, .

THE REORGANIZATION OF LONG-TERM MEMORY PROCESSES IN DIFFERENT


LEARNING PARADIGMS CONDITIONED FOOD AVERSION IN SNAILS
Nikitin V.P., Solntseva S.V., Filatova T.S., Nikitin P.V., Bredow D.V.,
Kozyrev S.A.,
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
v.nikitin @ nphys.ru
According to modern concepts, long-term memory may undergo
significant changes for a long time after training. However, the
mechanisms underlying these changes remain poorly understood. In the
present work, the mechanisms of reorganization of long-term memory in
conditioned food aversion snails at three different paradigms of
learning.
109

To develop the skill as a conditioned stimulus (CS) was used in


banana and reinforcing stimulus (US) served as an electrical current.
Trained animals showed a significant increase in latency periods of
reactions to the CS as compared to the control.
In the first series of experiments, the snails were trained for 3
days, presenting CS and US stimuli combined 6-10. Formed memory
rejection CS remained stable for at least 1.5 months, but the
properties of the memory during this time changed substantially. In
particular, 2 days after the learning impairment of memory
reconsolidation by NMDA glutamate receptor antagonist, MK-801 or the
protein synthesis inhibitor cycloheximide, injecting before reminder
the CS led to the development of resistant amnesia. Re-training of
these animals did not cause habit forming. Injection of MK-801 or
cycloheximide and a reminder 10 or 20 days after training had no effect
on the safety of memory. 30 days after training administration of MK801 or cycloheximide and reminder to induced amnesia development, but
at repeated training detected restoring memory. Thus, within 30 days
after the training is difficult, phase reorganization of memory,
including its consolidation during the first days of training,
stabilization and resistance to violate effects after 10 and 20 days
and re-acquired the ability to reconsolidation on the 30th day after
the training .
In the second series of experiments, the animals were trained
during the 1st day, presenting two combined stimulation CS and US at 30
min. 1 day after learning latent periods reactions to CS had more than
latencies reactions to food in untrained snails. On the 5th day after
the training latencies reactions to CS increased significantly. Thus,
within 5 days after the one-day training snails occurred gradual
spontaneous facilitation a skill that can be the result of "prolonged"
memory consolidation.
In the third series of experiments, the snails are bringing two of
co-stimulation CS and US with an interval of 12 days. After the first
combined stimulation CS and US revealed no aversive reactions to the
presentation of CS. Re- combined stimulation CS and US 12 days after
the first combination has led to the expression of aversive reactions
to the CS, which persisted for at least 14 days. Injection
cycloheximide or RNA synthesis inhibitor (-amanitin) immediately after
the first or second coupling stimulus induced suppression expression
skill. Thus, a single combination of CS and US is induction of latent
memory conditional food aversion which dependent on the processes of
translation and transcription.
The results indicate that at one and the same form of training can
be different in nature, dynamics and molecular mechanisms of memory
modification. The reorganization of the memory can occur spontaneously,
without any experimental interventions, and during the reconsolidation
of memory caused by her retrieval. Thus, the memory storage is complex,
dynamic process that continues long after the training or perhaps
throughout the period of remembrance, during which there is
consolidation or its extinction, the addition of new information,
interaction with other "traces" of memory.

110


- II - :
.
.., ..
-
.. , ,
lab_motiv@mail.ru

/
( S100b
- ) -II (A-II)


- .
, -
-II (
).

. , A-II

.
:
;
; .

A-II ( A-II S
100b) .
S100b A-II
.
,
S100bA-II
,

A-II.
- A-II,
, S100b, , ,

.


A-II, -,

.
,

(RAGE-),


. II, ,
, .
111

-II

-II,
-II. , -II

, /
- ,


.. .

NATIVE AND COUPLED WITH FUNCTIONAL DIFFERENT CARRIER


PROTEIN FORMS OF ANGIOTENSIN-II
UNDER HYPO- AND HYPERGLYCEMIA: COMPARATIVE ASPECTS.
Pevtsova E.I., Tolpygo S.M.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
lab_motiv@mail.ru
The effects of native and coupled with functionally different
proteins (neurospecific S100b and transport serum albumin
BSA)
angiotensin-II (A-II) administration on drinking instrumental behavior
and hemodynamics in rats under acute hypo-and hyperglycemia were
investigated.
We have previously shown that in hypo-and hyperglycemia clearly
reduced physiological activity free A-II (in terms of behavior and
hemodynamics). This results in reduction of its hypertensive effect and
suppression of drinking instrumental activities. It was found that the
most heavily influenced A-II realization suffers goal-directed behavior
in hyperglycemia. This is manifested in changes of instrumental
behavior on a number of factors: an increase in the latent period of
the act, increasing the duration of the consumption of water, increases
the time spent near the drinking bowl etc.
Hypoglycemia suppressed the activating effect of native and
coupled with BSA A-II (in contrast to A-II in a complex with S100b) on
learned drinking behavior. Native and coupled with the SA and S100b AII in hyperglycemia have inhibitory effect on drinking instrumental
act.
In the study of hemodynamic parameters the native and conjugated
with the BSA and S100b A-II as well as hypoglycemia and hyperglycemia
caused
the
decrease
of
the
hypertensive
effects
of
A-II was found. However, in some of animals physiological activity of
native A-II acute hypo-and hyperglycemia, bound with both SA and S100b,
on the contrary, strengthens critically, leading to death of animals as
a result of the progressive rise in heart rate and moderate
hypertension.
Thus, acute hypo-and hyperglycemia leveled functions of native and
bound with the various protein A-II, apparently due to allosteric
modulation of its interaction with specific receptors.
112

As well known, that increased glucose level is associated with


increased insulin secretion and leads to the formation of glycosylated
extracellular products that interact with nonspecific multiligand
receptor (RAGE-receptors), starting processes of free-radical compounds
and peroxide-oxidation of lipids within cells. Intracellular signal
transduction pathways A-II, glucose and insulin providing the formation
of free radical compounds are also interconnected. Thus, exogenous
administration of free and bound with proteins A-II increases the
formation of these compounds and triggers desensitization of specific
A-II receptors that underlies the reduction of physiological activity
of A-II. We can assume that A-II complexes with functionally different
proteins selectively included in the compensation of behavioral
disorders and hemodynamic appears due to acute and /or chronic shifts
of the constant blood glucose level by providing a plastic homeostatic
reorganization of regulatory processes and its fixation on the basis of
mechanisms of the so-called "metabolic memory".

-1
..
-
.. , ,
s.pertsov@mail.ru

,
,

( .., .., 2008).

,
-1
(-1)

. ,
-1
( .. .,
2009),
( .. ., 2009;
.. ., 2010). -1


. ,
..
, -1

.
, -1

(
113

.., 2010, 2011). ,




-1.
-1

.

-1
.
, -1
. ,
,
,

( .. .,
2007; .. ., 2011). -1

,
.

,
.
,

-1

,
( .. .,
2009, 2011; .. ., 2012).

Cu/Zn
. , -1


.

,
-1

.

INTERLEUKIN-1 IN THE CENTRAL MECHANISMS OF STRESS REACTIONS


Pertsov S.S.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
s.pertsov@mail.ru
Cytokines are endogenous polypeptide mediators of the cell-to-cell
interaction that provide the maintenance of cellular and tissue
homeostasis and contribute to the bodys defense reactions under the
114

influence of foreign factors and disruption of the tissue integrity


(Ketlinskii S.A., Simbirtsev A.S., 2008). Published data indicate that
cytokines, including interleukin-1 (IL-1), are involved in the stress
response of mammals. Our previous studies revealed that administration
of IL-1 to rats reorganizes the mechanisms for emotional evaluation of
negative emotiogenic factors (Pertsov S.S. et al., 2009) and prevents
pathological changes in the internal organs of animals under stress
conditions (Ivanova E.A. et al., 2009; Pertsov S.S. et al., 2010).
However, the role of IL-1 in neuroimmune interactions in mammals with
various behavioral characteristics and different resistance to stress
is poorly understood. Studies performed in the Laboratory for Systemic
Mechanisms of Emotional Stress (P.K. Anokhin Institute of Normal
Physiology, Russian Academy of Medical Sciences) were designed to
evaluate the central mechanisms for the involvement of IL-1 in
systemic reactions of the body in behaviorally passive and active rats
during stress exposures.
We showed that microiontophoretic application of IL-1 to nerve
cells in emotiogenic structures of the animals brain produces a
modulatory effect on pulse activity of neurons (Meshcheryakov A.F.,
2010, 2011). A negative emotiogenic exposure on the model of
ventromedial hypothalamic electrostimulation in rats was mainly
accompanied by an increase in the sensitivity of brain nerve cells to
IL-1. New data were obtained on the type of interaction between IL-1
and norepinephrine (one of the neurotransmitters and stress response
mediators) on neurons of the anteromedial cingulate cortex. The
incidence
of
inhibitory
reactions
of
cortical
neurons
to
microiontophoretic application of IL-1 after pretreatment with
norepinephrine was significantly increased in animals subjected to a
negative emotiogenic exposure.
Our experiments revealed that IL-1 plays an important role in the
neurotransmitter integration of negative emotional states. During and
after immobilization with electrocutaneous stimulation, behaviorally
active rats were characterized by a more significant activation of
noradrenergic processes in the dorsal hippocampus than passive
specimens (Umryukhin A.E. et al., 2007; Chekmareva N.Yu. et al., 2011).
An intraperitoneal injection of IL-1 had a stimulatory effect on the
release of norepinephrine in the dorsal hippocampus of active rats
during stress, but prevented an increase in the content of this
neurotransmitter in the post-stress period. This effect probably
contributes to the prevention of negative consequences of stress
exposure, which are developed during the post-stress period.
IL-1 was shown to be involved in the regulation of oxidative and
antioxidant processes in the hypothalamus, sensorimotor cortex, and
amygdala of rats under stress conditions (Pertsov S.S. et al., 2009,
2011; Kalinichenko L.S. et al., 2012). An intraperitoneal injection of
this cytokine produced a modulatory effect on antioxidant enzyme
activities (glutathione peroxidase, glutathione reductase, and Cu/Znsuperoxide dismutase), which was followed by a change in the oxidative
status of brain tissues in animals. IL-1 prevented the post-stress
activation of free radical processes and change in the antioxidant

115

protection of the sensorimotor cortex in behaviorally passive


specimens.
These data illustrate the specificity of central neurochemical and
neurophysiological mechanisms, which mediate the involvement of IL-1
in systemic organization of physiological functions in behaviorally
passive and active animals with different resistance to the same stress
factors.


-
.., .., ..
, ,

Vraevsky@mail.ru

WAGRij,

-,

.
D1 D2
, D1
dorsal caudate-putamen nucleus accumbens, core shell
D2 dorsal caudate-putamen.

,
. ,
,
.
.
, -
,
(SN),
.
: SN
.

WAGRij

, SN,
SN,
. ,
SN (
), , .
12-06-00746

116

THE DEATH OF DOPAMINERGIC NEURONS CAN BE ADAPTATION TO


ABSANS-EPILEPSY
Raevsky V.V., Birukova L.V., Sitnikova E.Yu.
Institute of the higher nervous activity and neurophysiology RAS,
Moscow, Russia
Vraevsky@mail.ru
The role of the dopaminergic system in the formation of a peak
wave discharges investigated in rats WAGRij, genetically predisposed to
absence-epilepsy Histochemical assay using antibodies to the D1 and D2
receptors determined reduction in the number of cells expressing D1
receptors in the dorsal caudate-putamen and nucleus accumbens, core and
shell area and expressing D2 receptors in the motor cortex and the
dorsal caudate-putamen. Analysis of the cellular composition of these
structures revealed a significant decrease in this period the total
number of neurons, accompanied by an increase in the number of glial
cells. However, statistical analysis showed no correlation between the
decrease in the number of neurons and the number of cells expressing
dopamine receptors. This indicates the termination of dopaminergic
receptor expression by neurons in these structures. It could be
expected that the reduction in various areas of the brain target
neurons ascending dopaminergic fibers will cause changes in the
cellular composition of the compact part of the substantia nigra (SN),
where dopaminergic cell bodies are located. Morphologic study confirmed
this hypothesis: the total number of neurons in the SN during period
from the first to the tenth month of life was significantly reduced.
Peak wave activity in WAGRij rats of the tenth month quite well
expressed. Pearson correlation analysis revealed a positive correlation
between the duration of epileptic discharges and the number of
dopaminergic neurons surviving in the compact part of the SN, that is,
the less survived neurons in SN, the less pronounced peak wave
activity. This suggests that reduction in the number of neurons of the
compact SN (dopaminergic cells) is an adaptive process, which prevents
the development of absence-epilepsy
This work was supported by grant of the RHSF number 12-06-00746

117

,

.
.., ..
, ,
romanovaga@mail.ru
,

,
.
,
, ,
75%
: ,
, .


,
,

.
,

,
,
.



CELEX. ()
7- .
Epson
Perfection V100 PHOTO.
. CELEX
(1 / / )
, .
CELEX
8,3 2,5 3
4,0 1,0 3 ( <0,05 U-). ,
CELEX

.

118

BEHAVIOURAL AND MORPHOLOGICAL DISTURBANCES INDUCED BY


BILATERAL PHOTOCHEMICAL THROMBOSIS
OF PREFRONTAL CORTEX IN RATS
Romanova

G.A., Shakova F.M.

FSBI Institute of General Pathology and Pathophysiology, Russian


Academy of Medical Sciences, Moscow, Russia
romanovaga@mail.ru
In recent years significantly increased the front of studies aimed
at understanding the pathogenesis of ischemic brain injury and the
search for pharmacological agents designed to stimulate the
regenerative processes in this pathology. These studies have not only
theoretical pathophysiological significance, but also of great
practical importance for the neurological clinic because it is known
that cerebral thrombosis is the cause of about 75% of strokes in
humans. In this case, an ischemic lesion of the frontal lobes are
almost always leads to cognitive disorders: impaired memory, learning
and analyzing the situation and significantly reduce quality of life.
Bilateral ischemic lesioning of the prefrontal cortex in rats by
phototrombosis, the convenient experimental model, was selected. This
model is sutable for selective investigation of cognitive disturbances
and lesion volumes which are reproducible from experiment to
experiment, that allows quantitative assessment of the extent of
ischemic brain damage obtained along with studies of the dynamics of
pathological and repair processes in the focus of ischemia. Our
previous studies demonstrated that photothrombosis of the cerebral
cortex in rats induced formation of local ischemic foci affecting the
whole thikness of the cortex, separated from the surrounding undamaged
tissue by a clear boundary.
The aim of this work was to examine behavioural disturbances and
morphological distructions in the brain cortex of rats after bilateral
photochemically induced thrombosis of the prefrontal cortex and to
study the effect of specific embryonal protein complex Celex. The
passive avoidance (PA) response latency was studied before and on the
7-th day after photothrombosis. The size of cortical ischemic
infarction was assessed on formaline fixed sections with slide examination of scanner Epson perfection V100 PHOTO. The photothrombosis
of rats prefrontal cortex provoked the deficit of passive avoidance
performance. Celex administrated intraperitoneally (1 mg/kg/day) for
seven postoperative days improved the performance in PA test.
The
morphological assessment the treatment with Celex caused statistically
significant diminution of the volume of the lesioned cortical tissues.
In these rats the mean total volume of the focal ischaemic lesion was
shown to be 8,32,5mm3. In the group of rats treated with Celex for 7
days
after photothrombotic lesion the volume of infarction cortical
area diminished to 4,01,0 mm3 (p<0,05 in U-test).
Celex had a pronounced neuroprotective effect during experimental
ischemic infarction of prefrontal cortex.
119


..1; ..2,3
1

. ..
-
.. , ,
3

o.kubryak@nphys.ru

. , (
),

.
.
. ..
40 ,
( 21- ) .
,
. 20 40
,
( )
(:
ST-150
Stabip STPL,
).

,
NIHSS, Rankin; ,
Berg, Bohannon, Perry, ,
: 2
30-
, .
:
.
.
. 21-

40 2 0
( ), NIHSS 3 1,
.
(p<0.005) 12%
.
38 , 42 .
5 40 .
,
20 ,
38 46 ( ~19%), 20
37 39 ( ~5%).
(p<0.005)
.
( 2 )
120



.
,
,

, ,
.
( 2456920),

ASSESSMENT OF THE VERTICAL STABILITY IN PATIENTS WITH ACUTE


DISTURBANCE OF CEREBRAL CIRCULATION
Romanova .V.1, Kubryak .V.2,3
1

M.F. Vladimirsky Moscow Regional Clinical and Research Institute


(MONIKI)
2
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
3
Research Center MERA
o.kubryak@nphys.ru

Objective: Assessment of the capacity of a patient who has


experienced acute disturbance of cerebral circulation (ADCC) for stable
vertical self-standing-and-walking using stabilometry with comparison
to the standard scales.
Technique: Observation was carried out in the MONIKI Department of
Neurology, following contemporary ethical norms, on 40 patients
undergoing planned medical rehabilitation after ADCC. All patients
received standard therapy, according to the up-to-day regulations; 20
of 40 patients therewith received additional treatment including
biological feedback as a support reaction of a patient (based on
stabilography) and the costume of axial loading using
original
modality (the national complex ST-150 of static stabilometry with
software variants Stabip and STPL, and the Regent costume for axial
loading).
Complex
testing
was
performed
including
consecutive
application of standard scales for general assessment of patients
condition (NIHSS, Rankin) and coordination, body balance control
according to Berg, Bohannon, Perry, and Stolyarova as well as a simple
(not complicated) Rombergs test on the stable platform: 2 consecutive
30-second phases of quiet vertical standing (with open and closed eyes)
in the European feet position. All patients underwent such testing
twice: at the days of the beginning and the end of rehabilitation.
Standard methods were used for statistical processing of the data
obtained.
Results: According to the outcome of the 21- day rehabilitation
course, the general condition of the majority of patients improved: by
the Rankins scale, the mean score in the group of 40 patients
decreased to the end of rehabilitation course from 2 t 0 (absence of
symptoms), and by
NIHSS scale from 3 t 1. In the group of
121

observation, a statistically significant (p<0.005) improvement of


scores by the Berg scale was noted on the average, by 12% from the
initial values for the whole group. At the start of the treatment, the
mean score by Berg scale for all patients was 38 and at the end of the
course 42. In this case, in 5 of 40 patients, the Berg scale score
didnt change. It should be noted that dynamics of the Berg scale score
growth was better seen in 20 patients who received additional therapy
(the mean score increased from 38 to 46, by ~19%) vs. 37 to 39 (by ~5%)
among the rest 20 patients.
Statistically significant (p<0.005)
decrease of the power input index during the stabilometric
investigation was seen to the end of the course as compared to the
initial indices. In the overwhelming majority of cases (except for 2 of
them), decrease of the power input index while quietly standing with
closed eyes corresponded to increase of the Berg scale score as it was
shown by stabilometry data.
Conclusions: Its counterproductive to consider interrelations
between instrumental measures of the vertical stability and widely used
assessment scales in terms of only simple correlations because the
score differences in this case are due to both subjectivity present in
patients assessment by a physician and specificity of methods or test
conditions. The novel stabilometry index (power input index)
(Patent RF No. 2456920) is a relevant characteristic of stability in
ADCC patients during quiet standing.

,

.., ..
, ,
sergutina.anven@yandex.ru


. ,
, () ()

.
,

, .

,
, .

( III V , , ,
( 3)

"
".

(Karnovsky, Roots,
1964) . ,
122

() ("Serva").
,

- 3 (, ) 2,5 ,
488 .
,
(One-wayANOVA).
,


. ,

, .

(
)
III

.


" ".

"invivo".

CYTOCHEMICAL INDEX OF ACETYLCHOLINE ESTERASE ACTIVITY THAT


WAS STUDIED IN THE BRAIN OF WISTAR AND AUGUST RATS
Sergutina A.V., Rakhmanova V.I.
Research Center of Neurology, Russian Academy of Medical Sciences,
Moscow, Russia
sergutina.anven@yandex.ru
Typological and individual
peculiarities of central nervous
system metabolism have the large importance
in adaptive and
pathological processes. These peculiarities are studied in strain
animals including rats predisposed (August) and resistant (Wistar) to
emotional stress. However, the peculiarities of acetylcholine system,
which is one of principal neurotransmitter systems in behaviour regulation of
strain animals, are studied insufficiently.
The purpose of the present work is to do a quantitative
cytochemical investigation of acetylcholine esterase activity, which is
acetylcholine catabolism enzyme, in the brain structures of Wistar and
August rats.
Quantitative cytochemical methods were used for measurement of
acetylcholine esterase (AChE) activities in the brain structures
(sensorimotor cortex (layers III and V), nucleus caudatus, nucleus
123

accumbens and hippocampus (CA3 field) of Wistar and August rats with
high and low levels of motor activities in "open field" test.
Acetylcholine esterase activity revealed in freezing brain section
histochemically (Karnovsky, Roots, 1964). In the present investigation
was used tetraisopropilpirophosphoramide ("Serva") for inhibition of
non-specific choline esterase and esterase activities. Quantitative
valuation of acetylcholine esterase activity was performed the discrete
method. The levels of optical dense in the product of histochemical
reaction were measured on microscope LUMAM-I 3 (LOMO, Russia). The
sound (diameter 2,5 mkm) and filter ( wave-length 488 nm) were used.
Received data were processing statistically, and one-factor dispersion
analysis (One-way ANOVA) was used.
It was found that acetylcholine esterase activities in indicated
brain structures of August rats with high levels of motor activities
prevail over August rats with low levels of motor activities. No this
clear was noticed in Wistar rats and it was shown that distinctions
between animals with high and low levels of motor activities were
slight, but these distinctions vary depending on series of the
investigations. Interstrain comparison of August rats with low levels
of motor activities and Wistar rats with high levels of motor
activities ( greatest distinct of motor function in these animals)
showed exceeding of acetylcholine esterase activities in layer III
sensorimotor cortex on August rats brain and no distinctions were
noticed in the other indicated brain structures these animals.
Thus, typological and individual peculiarities in the brain of
Wistar and August rats were revealed on cytochemical index
"
acetylcholine esterase activity".
Our data can be important to selection of experimental models for
investigations of brain plasticity "in vivo".



.., .., .., .., ..,
..
-
.. , ,
v.nikitin@nphys.ru

,
NMDA .
, -
. (3-
)


. .
124

(10 )
. ,
,
,
/ .
( 13-04-01540).

THE ROLE OF DNA METHYLATION PROCESSES IN THE MECHANISMS OF


AMNESIA AND MEMORY RECOVERY CONDITIONED FOOD AVERSION
Solntseva S.V., Filatova T.S., Nikitin P.V., Bredow D.V., Kozyrev S.A.,
Nikitin V.P.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
v.nikitin @ nphys.ru
Investigated the processes involved of the mechanisms of DNA
methylation in amnesia induced violation of reconsolidation memory of
conditioned food aversion antagonist of NMDA glutamate receptors in
snails. It was found that the effects of inhibitors of DNA
methyltransferases depended on the stage of amnesia. In the early
stages of amnesia (the third day after its induction) injection
methyltransferase inhibitors are combined with a reminder conditioned
food stimulus led to recovery of memory. Applications of inhibitors
without a reminder were not effective. In the later stage of amnesia
(10 day) methyltransferase inhibitors had no effect on its development.
It is suggested that the presentation of reminder stimuli leads to
reactivation processes involved in the development of amnesia, one of
the key mechanisms which is the methylation / demethylation of DNA of
nerve cells.
This work was supported by grant of RFBR (project 13-04-01540).


-

..,

..

-
.. , ,
n.solovyeva@nphys.ru

: 1) ()
, ()
, 2) -
125

() ,
3)
(Luskin MB, Neuron,1993, Lois C , AlvarezBuylla A, Science, 1994).
,
,

(So et al, Neurosci, 2008).



, , ,
,
.
.
C57BL/6 8
(). 1

5--2'- () (50/,
/).



.

.
2
4-

- ,
.
3-

,
,
- .

BrdU-positive cells
.
,

,
,
,
.

EARLY OLFACTORY LEARNING STIMULATES MIGRATION OF PROGENITOR


INTERNEURONS FROM THE ROSTRAL MIGRATORY TO THE OLFACTORY
BULBS.
Solovjeva N.A., Anokhin K.V.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
n.solovyeva@nphys.ru
Neurogenesis of the bulbar interneurons passes through three
stage: 1) the stage of progenitor cells generation (PC) from stem cells
located in the anterior subventricular zone (SVZ)
of
the brain
lateral ventricles, 2) the stage of the migration of PC via the rostral
migratory stream (RMS) in the olfactory bulb, and
their radial
migration to the site of the dislocation and 3) the stage final
differentiation in granular and glomerular interneurons
(Luskin MB,
Neuron, 1993, Lois C , Alvarez-Buylla A, Science, 1994). It was
126

established that early olfactory learning stimulates generation of PC


in the SVZ with the resulting increase of a number of newborn neurons
in the olfactory bulbs (So et al, Neurosci, 2008). It is tempting to
suggest that this learning-dependent regulation might take place not
only during generation of the PC but also during their migration and
differentiation. The present study was undertaken to test this
hypothesis.
Pups of the C57BL/6 mice (PD8) were trained for passive avoidance
of a polecat odor. One hour before training pups were injected with
the marker of DNA synthesis 5- bromo-2'-deoxyuridine (BrdU) in a dose
50 mg/kg, i.p. Detection of BrdU incorporation into PC was performed
by means of fluorescent immunohistochemistry. The study was carried out
in accord with bioethics committee rules. At 2 hour after learning a 4fold increase of number BrdU-positive cells that migrated out of a
rostral extension of RMS was observed in experimental pups in
comparison to untrained pups. As a result a large aggregate of PC was
formed at third day after training in a nuclear region of the olfactory
bulb. Cells from this region rapidly migrated into glomerular and
granular layers, mainly into an odor-specific region of the olfactory
bulb. This rapid migration was supported by a significant increase of a
number of BrdU-positive cells in layers of trained pups in comparison
to the control group.
Our results suggest that olfactory training in an early postnatal
period can stimulate the migration of PC in the olfactory bulbs and
thereby contribute to increased
formation of new interneurons which
subsequently can be incorporated into olfactory bulb neuronal networks.

,

.., .., ..
-
.. , ,
s-sudakov@nphys.ru

.
.
,
,
- .

.
, ,
,
127

.
,
. , 7

. 12-14
- , ,
. , . ,

.

-,
.
,
, .

CHANGE OF SENSITIVITY TO THE ACTION OF ETHANOL IN RATS


CHRONICALLY TREATED WITH NICOTINE
Sudakov S. K. Nazarova G.A. Alekseeva E.V.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
s-sudakov@nphys.ru
Joint use of nicotine and ethanol is widespread among humans. Most
often against a background of chronic tobacco smoking is episodic
consumption of alcoholic beverages. Aware that chronic nicotine
enhances self-administration of ethanol in rats, which may indicate a
change in the perception of positive reinforsing properties of ethanol.
One of the component of reinforcing
action of ethanol is its
anxiolytic properties. This work studied the severity of anxiolytic
action of ethanol, as well as its effects on metabolism, motor
activity, and eating and drinking behavior of rats chronically injected
with nicotine. Introduction of ethanol in animals led to significantly
lower anxiolytic effect, compared with the effect of ethanol in the
intact rats. In addition, 7 hours after administration of ethanol there
were decline intensity of metabolism and decreased motor activity.
During 12-14 hours after administration of ethanol in nicotinedependent rats, as well as in intact, there was suppression of feeding
and drinking behavior. Moreover, drinking behavior in nicotinedependent rats was more suppressed.
Thus, chronic nicotine intake
leads to suppression of sensitivity of animals to the anxiolytic action
of ethanol. This may lead to a decrease in sensitivity to reinforcing,
pleasurable effects of ethanol. The negative action of ethanol on
metabolism, motor activity and drinking behavior in rats chronically
consuming nicotine were increased.

128


. .
.

,
galsansukhbat@yahoo.com

: ,

.
,
,
.



.
, , ,
.
,
/

. :



. . .
:
1.

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2.
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3.


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( 21 27
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( . . c) (,
\) .

SensoStarGL30

SPSS 18.
.

:
(, \)
64 2.8 \,

143
129

4.1 \. ( 0.
001)

223 10
\., .



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, :


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128 4. .. 57 7 ..
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,
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(121.5. \) 5
(2.4 0.6 \) .



.
,
,
.
, 37- .

1,01,5 --1 (15 30 %)
.
56 -1 ,
20 --1 .



,
. ,

.
130

,
, ,
.


,
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. .
.
: 1. ,

.
2.



.
3.

.
.
,
.

THE STUDY OF TRAINING PROCESS IN SPORTSMAN BY


P.K. ANOKHINS THEORY OF THE FUNCTIONAL SYSTEM
Sukhbat G.
Avarga Institute of physical culture and sport,
galsansukhbat@yahoo.com

Mongolia

Background and aim: Assessment of the physical capacities of


athletes is one of the most important issues in modern sports and this
capacity is closely linked to training process in sportsmen. Anokhin's
theory of the functional system is based on the concept of the useful
result as the system- forming factor. Therefore the aim of our
research was to study anaerobic capacity and training process in
boxers by P. K Anokin s theory of the functional system.
Materials and methods: The Boxers of elite classes have been
studied during their training process. Hemodynamic parameters
such
as arterial blood pressure ( systolic and diastolic ) and pulse rate
have been determined by monitor
and
lactate in blood by lactate analyze - SensoStar GL30
in
calm period and 1.2.3 loads periods
and period of excitement.
The results of current research had
been analyzed by soft we program- SPSS- 17.
Results and conclusions: The hemodynamic parameters in elite
boxers
such as arterial blood pressure ( systolic and diastolic )
and pulse rate and lactate concentration in blood in various
131

periods
of training process show that
sports system quantum as
well as optimal
training process .
The obtained
results
of
anaerobic working capacity and hemodynamic parameters in athletes
(elite
boxers ) in various period of their training
had been
explained by P. K Anokin s theory of the functional system of
human organism
such as useful result as the system- forming factor.



..1, ..1, ..1, ..
1

1,2

-
.. , ,
nphys@nphys.ru
2
-, ,
nrcki@nrcki.ru

,

.

.
(),
(Gibbs et al., 2008).
, ,
,
(Barber et al., 1997).

.

,
.
.
267 (19.06.2003.), "
" ( . ..
, 1 3.09.2005 .).
1-2 ,
3-5 .
:

2,

5--2-,

NMDA 5 801. 648 .


. -
-

2-

132


, . 801
. ,
5--2-
,
. ,
,
, .
5--2-
.
, 50

. ,

, 5--2-,
.
;
,
, ,
.
.
NMDA ,
.
, , , ,
. , -,
, .

SYSTEM AND CELLULAR MECHANISMS OF AVERSION IN NEWBORN CHICKS


Tiunova ..1, Bezryadnov D.V.1, Komissarova N.V.1, Anokhin .V.
1

1,2

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


nphys@nphys.ru
2
NBICS Center, NRC Kurchatov Institute, Moscow, Russia,
nrcki@nrcki.ru

In the present work we studied mechanisms of two similar one-trial


learning models which address to the feeding behavior in newborn
chicks. Both types of learning are based on the inborn predisposition
of young chicks to peck readily on small objects and to memorize their
visual and gustatory characteristics. In passive avoidance training,
memory develops as a result of single peck at a novel object (bead)
covered by a distasteful substance (Gibbs et al., 2008). During
conditioned taste aversion training, memory also is formed after chicks
peck at a bead, but neutral (dry) one, and subsequently are made sick
by intraperitoneal injection of lithium chloride (Barber et al., 1997).
In both models training results in avoidance of the aversive object
during subsequent presentations. The aim of the present work was to
compare mechanisms of memory consolidation in passive avoidance and
taste aversion models by means of administration of glutamate receptors
133

antagonists and protein or DNA synthesis inhibitors around the


training.
Method. All experimental protocols were performed in accordance
with the RF Ministry of Health order Nr.267 and Guidance to works
involving animals in experiments (P.K.Anokhin Institute of Normal
Physiology, RAMS, Protocol Nr.1, 3.09.2005). The chicks were trained
for conditioned aversion to a bead or passive avoidance at the age of
1-2 days, or for conditioned taste aversion to novel food at the age of
3-5 days. At different time intervals before or after training the
chicks received intraventricular or intraperitoneal injections of one
of the following: inhibitor of protein synthesis anisomycin, of
glycoprotein synthesis 2-deoxygalactose, of DNA synthesis 5-iodo-2deoxyuridine, antagonists of glutamate NMDA receptors AP5 and MK801.
The animals were tested 6 to 48 h after the training.
Results. In both learning models, passive avoidance and
conditioned aversion to bead, memory was impaired by pre-training
administration of anisomycin or 2-deoxygalactose. Injection of
anisomycin just after training disrupted memory in passive avoidance
but not in conditioned aversion task. Pre-training administration of
MK801 impaired memory in both tasks. On the other hand, administration
of DNA synthesis inhibitor 5-iodo-2-deoxyuridine disrupted memory in
conditioned bead aversion task but not in the passive avoidance. We
hypothesized that this divergence might be due to the peculiarity of
conditioned aversion learning which involves not only behavioral
functional systems but metabolic systems as well. In further
experiments
we
checked
the
effect
of
5-iodo-2-deoxyuridine
administration on conditioned taste aversion to novel food. We found
that the inhibitor injection 50 min after the food intake significantly
reduced the latency of pecking start during test. However, the amount
of the consumed food did not differ between animals receiving 5-iodo2-deoxyuridine and controls. This discrepancy might be produced by
recovery
of
the
impaired
memory
owing
to
gustatory
input;
alternatively, DNA synthesis inhibitor might disrupt memory for visual
but not gustatory features of the food that caused sickness.
Conclusion. Conditioned taste aversion, as well as passive
avoidance learning, involves activation of NMDA receptors and protein
synthesis. At the same time, consolidation of conditioned aversion
memory requires DNA synthesis which is possibly attributable to system
mechanisms of this learning task. Administration of DNA synthesis
inhibitor apparently impairs memory for visual cues but not for
gustatory characteristics of the food.

134

-
.., ..
-
.. , ,
stolpygo@mail.ru



- ().

- -II (A-II),

A-II

(1 2-),
(Alzet,),
7 .
,
A-II ( 7 )

. 1
2-
. 1-

,
7 .

,

. 2-

PD
123,319

,
14 .
,
(
). -
,
, ,

(NO) NO-,
, ,
, .

.

,
1-
,
NO-
NO . A-II
2- PD 123,319
135

, .

PD 123,319

- ,
.
,

- ,

,
, 1. ,
, ,
-
,
-,

2-.
( 110600847).

ALCOHOL MOTIVATION THROUGHOUT RENIN-ANGIOTENSIN SYSTEM


ACTIVITY MODULATION
Tolpygo S.M., Pevtsova E.I.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
stolpygo@mail.ru
In experiments with formed alcohol dependence dynamic of several
immunological and biochemical parameters throughout directed modulation
activity of renin-angiotensin system (RAS) was studied in rats. This
modulation performed by activation or blockade of specific receptors to
more active peptide RAS - angiotensin-II (A-II) during prolonged
administration of A-II or antagonists its receptors (AT1, AT2
receptors). Osmotic minipumps (Alzet, USA), providing a continuously
supply of a substance in body within 7 days in experiments were used.
It was revealed that in rats with formed alcohol motivation RAS
activation by prolonged administration A-II significantly increased
consumption of ethanol and reduced water intake. Reduced activity of
RAS by blockade of AT1 and AT2 receptors resulted to contrary changes
in consumption of water and ethanol. Prolonged administration of the
AT1 receptor antagonist losartan caused moderate reduction in
consumed of total volume of fluid (alcohol, water) after osmotic
minipumps implantation, and within next following 14 days. Consistent
reduction in water consumption, combined with a significant increase in
alcohol consumption as a definitive effect of minipumps was detected.
With long-term administration of AT2 receptor antagonist PD 123,319
decline in the amount of ethanol consumption was observed.
In our experiments the chronic alcoholization stemmed to
development of non-specific immune deficiency (blood cytological
indicators) which was exhibited in rats. It was combined with increase
in enzyme activity of damage markers in liver and myocardium, high
lipid peroxidation, depletion of antioxidant protection, as well as
impairment of nitric oxide (NO) synthesis and high activity of NOsynthase, shifting with production of reactive oxygen. Under directed
136

modulation RAS activity phase changes of humoral and cellular immunity


was identified. In a free choice between ethanol solution and water, as
well as prolonged administration of the AT1 receptor antagonist
losartan it was observed an expressed normalization of immune status
and reduction of imbalance NO-synthase activity in cells and level of
NO production in blood plasma of rats. After prolonged administration
of A-II and AT2 receptor blocker PD 123,319, these changes have been
increased and become more pronounced than in forced alcoholization of
animals. After prolonged administration PD 123,319 significant increase
in activity significant myocardial form lactatedehydrogenase hydroxybutiratdehydrogenase, indicating ischemic myocardial damage and
vascular endothelium were registered. Changes in regulation of water
and salt balance in the body, as well as shifts and changes in the
immune system, nitric oxide, induced by chronic alcoholization are
mediated primarily through the activation of AT1 receptor suggested.
Data of evidence that increasing of the toxic effects of alcohol on
organs and tissues, resulting in damage to the internal organs,
primarily cardiovascular system, was related to reduced activity of AII AT2 receptors.
Work was supported by grant RFH ( 11-06-00847a).



.., ..
, , ,
udutv@mail.ru

, ,
, ,
, ,
()

.
,
.
(),

, ,
,

.
:


.
137

:
21 45 (27,37,4 )
(31,45,6 ).
(..1110444) :
(); , ;
; ;

2;
;

;
; ; D-; ; XIII-;
; ; ; -; 4, 8, 1.

() ( N98251, N106518, N107929),
(V=0,45)

,
.
:
-(60%), -(20%) -(20%)
. ,


, -
.
- - .

, , ,
.
,
.
: ,

Point-of-care testing.

.
, ,
(
),

,
.
.
:
.

138

A NEW PARADIGM FOR EVALUATION OF FUNCTIONAL STATE OF BLOOD


HEMOSTATIC POTENTIAL
Udut V.V., Tutrin I.I.
Federal Governmental Budgetary Institution Research Institute of
Pharmacology Siberian Branch of the RAMS, Tomsk, Russian Federation,
udutv@mail.ru
Governmental Budgetary Educational Institution of Higher Professional
Education Siberian Medical State University of Russian Federation
Ministry of Health, Tomsk, Russian Federation
The majority of clinical research, except, probably, critical
states monitoring, is associated with getting contradictory data on
hemostatic potential (GP) under different diseases, despite its
measurement is universal and relatively non-specific. Exactly the
mentioned fact demands elaboration of new approaches of analysis and
data interpretation. A system regulating an aggregation state of blood
is the system able to mobilize its elements in compliance with
momentary functional demands to ensure optimal GP. Axiomatic nature of
its evaluation is known. This fact creates a priority of using a
systemic approach, which enables getting objective information on
interaction
between
anatomical,
morphological
and
biochemical
structural elements of the system.
The aim of the work: To elaborate and to test in clinics an
integrative technique for estimating the functional state of the
hemostatic potential in comparison with generally accepted methods for
estimation of the hemostatic system and endothelial function.
Methods: Investigations were carried out on healthy volunteers of
both sexes at the age of 21-45 years (an average age was 27,37,4
years) as well as on patients with blood coagulant activity disorders
(an average age was 31,45,6 years). At the regime of determining
thrombodanger (SU1110444) the following tests were carried out:
thrombin generation test (TGT); measurements of a series of integrins,
selectins
and
cadherins;
spontaneous
and
induced
thrombocyte
aggregation tests; measurement of von Willebrand factor, thromboxane
A2, activated partial thromboplastin time, thrombin time, prothrombin
time,
fibrinigen,
soluble
fibrin
monomer
complex,
D-dimers,
fibrinolytic activity, XIII-factor, plasminogen, endothelin, C-reactive
protein, tumor necrosis factor-, interleukines 4, 8 and 1. We used
low-frequency haemoviscoelastography (Patents 98251, 106518, 107929)
method, which enables detailed estimation of all blood clotting stages,
anticoagulant and fibrinolytic activity in the whole blood (V=0,45 ml).
Results: GP estimation by haemoviscoelastography made it possible
to typify GP values into normal (60%), hypocoagulation (20%) and
hypercoagulation (20%) levels. None of the analyzed clotting,
fluorimetric and immunoenzyme methods of getting information about
endothelium-produced substances and hemostatic factors doesnt stratify
into the mentioned GP types either due to a wide range of the reference
values of the measured substances or due to their trace quantities.
Only TGT results showed possibility of revealing GP hypo- and
139

hyperactivity.
Investigations
at
the
regime
of
determining
thrombodanger enabled revealing trends in reactions of the overall
tests, which are considered to be low-informative in terms of
laboratory diagnostics. Identical results were obtained also when
studying patients with hemostatic system disorders declared themselves
as thrombotic complications.
Conclusion: Conclusion: Received information showed that for HP
estimation the study should be carried out in whole blood and in the
regime of Point-of-care testing. Only such approach allows evaluating
the total of system RASB elements interactions under the influence of
inescapable stressor - standardized contact activation. Indeed, the
whole blood sample containing aliquots of endothelium producers (a
number of which realizes effects in the limited time interval), blood
cells and hemostasis factors being used for operating analysis allows
obtaining objective information about the "time sample" of HP state.
Two-fold study of HP: before and after the test of " thrombosis risk"
is the best variant to receive objective data.




.., .., ..
-
.. , ,
n.fudin@mail.ru

()
.
19 18-27
.
,
-

.

(
), .
6 .
Sports Art 5005,

--8
(, ).

, (/) , 1/, ( . ),
(V, /)
SIGMA bc-509 (Germany),
140

, .
.

(.. ),

( )
.
( )
( .., 1984).
:

,

.

. ,
(p<0,05),
, ,
, , , (p<0,05),
(p<0,05), (p<0,05), (p<0,05).
,
,
1-
(p<0,05). ,
6-
, (p<0,05).
,


(p<0,05),
.
(p<0,05),
,
.
:

.

LOCAL RHYTHMIC THERMAL EFFECTS AS THE MEANS OF THE


REHABILITATION OF SPORTSMEN'S PHYSIOLOGICAL FUNCTIONS AFTER
INTENSIVE PHYSICAL ACTIVITY
Fudin N.A., Klassina S.Ya., Vaguine YU.Ye.
P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia
n.fudin@mail.ru
The present paper is devoted to the problem of physical functions
rehabilitation after physical activity in different conditions. During
the research, two experiments were held that resulted into analysis of
recreation with thermal influence and without it.
19 sportsmen aged from 18 to 27 years were involved in the first
experiment where they rotate the bicycle ergometer pedals with
141

gradually increasing resistance of rotation until the refusal to


continue. After the work sportsmen physical functions rehabilitated
while seating for 6 minutes. Then the sportsmen started working again
until another refusal to pedal. During the second experiment, the same
participants did the same procedure, but in the rehabilitation period,
the nose and mouth area was be heated by rhythmic thermal actions.
Analysis of received data was based on the K.V. Sudakov concept of
systemic quantization of goal-full behavior. Each stage of the
experiment was be analyzed separately. Each stage's result was
characterized by its parameter (deviation of the velocity of pedal
rotation from a given velocity) and had the physiological price
(Klassina S.Ya., 1984).
First, under the intensive physical activity the sportsmen of both
experiments complained of bad feelings. Blood pressure, heart beat
rate, Kerdo autonomic index and cardiac output raised. The increase of
the physiologic parameters indicated the augmentation of sympathetic
nervous system tone.
Second, the physiologic processes normalized faster with the local
rhythmic thermal influence than without it. Between two groups of data
the statistical significant difference was found (p<0.05). The
sportsmen felt better to their minds.
Then, in the second stage of hard work which was after the
rehabilitation period with the local rhythmic thermal impact there was
less deviation of systemic physiologic parameters (parameter of result
and physiological price) in comparison to one in the condition of the
first experiment without thermal influence. The statistical significant
difference was found between these groups of data also (p<0.05).
To conclude, the local rhythmic thermal influence was the
effective non-medicinal method to rehabilitate the sportsmen after
intensive physical activity.

..1,2, ..1
1

,
2
. .. , ,

septitchi@mail.ru



.

, , ,
,
142

.

,

.
-,
. ( 18-19 )
6 ,
( AIN-93G
). ,


in situ (single-pass intestinal perfusion).
.
,

,
10-20 %
,
.
,

. 6

(Jmax) ( 3,5 ),
(Kd) ( 2 ) (Kt),
(Jmax/Kt)
( 4,6 ). 3

( 3,4 )
, 6 ,
.
4 - 5
,
3
, , .
6


1,5 ,
3,6 , .



.
11.817.09.01 F.

143

THE ABSORPTION OF MONOSACCHARIDES IN THE SMALL INTESTINE


OF RATS KEPT ON A CARBOHYDRATE FREE DIET
IN EARLY POSTNATAL ONTOGENESIS
Sheptitsky V.A.1,2, Ceban L.N.1
1

The Institute of Physiology and Sanocreatology of the Academy of


Sciences of Moldova, Chisinau
2
The Transnistrian State University "T.G.Shevchenko", Tiraspol, the
Republic of Moldova
septitchi@mail.ru
Some forcible arguments for the presence of regular response of
the monosaccharide transport systems in the small intestine to
carbohydrate content changes in the dietary intake have been obtained
in the last decades. Nevertheless, some peculiarities and the
mechanisms of this adaptive response remain debatable. That can be
explained, in particular, by the variety of used methodical approaches,
by the differences in age of the experimental animals and in action
time of the nutritive factors. Despite the fact that carbohydrate free
diet and the period of withdrawal from it are a good model for the
investigation of natural laws and mechanisms of the formation of
adaptive and pathogenic changes of the small intestine transport
systems' activity, the impact of carbohydrate free diet in the period
of early postnatal ontogenesis upon the absorption of monosaccharides
has not been studied sufficiently.
The aim of this work is the investigation of glucose and
fructose absorption in the small intestine of rats kept on a
carbohydrate
free
diet
in
the
period
of early
postnatal
ontogenesis outright from the moment of transition to definitive
nutrition.
The research has been carried out using male rats kept in the
conditions of an animal house. After weaning (on day 18-19), the young
rats of the experimental group were on carbohydrate free diet during 6
weeks. Then, a part of the animals were put on the standard food ration
(the diet AIN-93G with modifications). The reference group comprised
the animals that were kept after weaning on the standard food ration.
To assess the absorption of monosaccharides, the method of single-pass
intestinal perfusion of an isolated segment of the small intestine in
situ was used. The experiments with the use of animals have been
carried out with observance of the bioethical norms and rules.
It has been revealed that, in rats kept on the carbohydrate free
diet after weaning, the intensity of glucose absorption is only 10-20%
of this index value in the reference group animals depending on the
substratum's initial concentration in the intestinal cavity and
fructose absorption is practically absent. According to the data
obtained in the experiments with the use of floridzin, the change of
glucose absorption in the conditions of carbohydrate free diet takes
place because of a sharp decrease of the active component of its
transport. After 6 weeks of the animals' carbohydrate free diet, a
considerable decrease of the maximum glucose transport rate (Jmax) (in
144

3.5 times), an increase of the nonsaturable absorption rate constant


(Kd) (almost in 2 times) and the Michaelis' constant (Kt), a decrease of
the active
glucose
transport
system's
effectiveness
coefficient (Jmax/Kt) (in 4.6 times) were observed. As early as in 3 days
after putting the animals from the carbohydrate free diet on the
standard food ration, a noticeable increase of the glucose absorption
intensity (in 3.4 times) in comparison with the absorption level in the
rats kept on the carbohydrate free diet during 6 weeks as well as the
possibility to mention some minor level of fructose absorption
occurred. In the course of the subsequent 4-5 weeks, the intensity of
monosaccharide absorption had been somewhat increasing in comparison
with the absorption level in the rats kept on the standard food ration
for 3 days after their withdrawal from the carbohydrate free diet.
However, it had not reached the level of the reference group. In 6
weeks after putting the animals from the carbohydrate free diet on the
standard food ration, the glucose absorption rate was in 1.5 times
whereas the fructose absorption one - in 3.6 times less than the
corresponding values of the reference group.
Thus, a prolonged carbohydrate free diet in early postnatal
ontogenesis substantially reduces the absorption of monosaccharides in
the small intestine and is conductive to the development of
malabsorption in the subsequent life.
The work has been fulfilled in the framework of the project
11.817.09.01 F.




..1, .. 1*, .2., .1.,
.1., .. 1
1

-
.. , ,
v.sherstnev@nphys.ru
2

,
Wistar
.

c-fos , NeuN

D-28K


.

NeuN.
NeuN+ - +
145

, c-fos .
c-fos
NeuN

.
,

,
,


.
, 12-06-00077

DIFFERENT POPULATIONS OF NEURONS IN RELEVANT BRAIN STRUCTURES


SELECTIVELY ARE ENGAGED IN LONG TERM SPATIAL MEMORY
MAINTENANCE
V.V.Sherstnev1, M.A.Gruden1*, Ju.I.Alexandrov2, Z.I.Storozheva1,
O.N.Golubeva1, A.T.Proshin1
1

P.K. Anokhin Institute of Normal Physiology RAMS, Moscow, Russia


v.sherstnev@nphys.ru
2
Institute of psychology RAN

Particularities in supplying of long term memory processes of


various neural populations located in relevant brain structurs were
investigated. Expression of transcription factor c-fos in cells which
synthesized neuronspecific proteins NeuN and calbindin D-28K in the
hypocampus, cerebellar vermis, motor and retrospinial cortex after
training to find hidden platform in water maze was investigated by
immunohistochemical method. Apoptotic neural cells expressed NeuN were
also revealed. Significant differences in intra - and interstructural
distribution of the NeuN- and calbindin - positive neurons which
expressed c-fos in trained and control rats were examined. Correlation
between quantity of c-fos expressed NeuN positive neurons in the brain
retrospinial cortex and undicators of long term spatial memory
consolidation was disclosed. Obtained data are of evidence that neurons
from different neural populations in relevant brain structures
selectively are engaged in long term spatial memory maintaince.
Support by RFBR, grant 12-06-00077.

146

WAG/RIJ
.. , . .
. .

ihna_ann@mail.ru

WAG/Rij,
-,

.
.
: 1-3, 4-6, 7-9, 10-12, 13-15
. .

4 , ,
. 10
.

(1),

(,
, ), ,
. ,
( 1 )
(, , ,
.).
(86/609/)
.
.
WAG/Rij
. WAG/Rij
1
, 1
1- 3- . 4-5
1 ,
. 1- 4-
WAG/Rij ,

.

WAG/Rij
,
. WAG/Rij
, : 55%
(
23% ). ,
WAG/Rij, , .
WAG/Rij
( 66% )
( 27%
).
147

,
WAG/Rij
,
,
.

WAG/Rij.
13-04-00741

THE MATERNAL BEHAVIOR IN WAG/RIJ RATS


Shishelova A.Yu., D.A. Tsvetaeva
Institute of Higher Nervous Activity and Neurophysiology of RAS,
Moscow, Russia
ihna_ann@mail.ru
The present study examined the maternal behavior in WAG/Rij rats
derived from Wistar rats as a genetic model of nonconvulsive absence
epilepsy.
Methods. The maternal behavior tests were conducted on 1-3, 4-6,
7-9, 10-12, 13-15 Days postpartum. Each litter was contained in
individual cage. The test procedure included short mother separation (4
min), short handling of pups, mother placing in home cage and video
observation of dam behavior in during 10 min.
We recorded latencies of first pups approach (LP1), pup retrieval
and nest return, the sum duration of active contacts with pups
(sniffing, licking, retrieval), the duration of nest building, pups
retrieval pattern, occurrence of lasting (> 1 min) manifestations of
different mothers behaviors (grooming, water drinking, one pup
retrieval, rotation). The experiments are executed in compliance with
requisition of The Directive of European Union about using of animals
for experimental investigations.
Results. Comparison of WAG/Rij with Wistar rats reveal strain
effect on maternal behavior. The behavior reactions of WAG/Rij and
Wistar rats after a nest disturbance was different. Most of WAG/Rij
female rats had the variations of LP1 between the investigated rearing
periods whereas LP1 in Wistar females smoothly decreased from first to
third period. Then LP1 increased in most of Wistar mothers, what
coincided with fall of pups needs in constant mother care. From first
to fourth period of rearing WAG/Rij rats had less active contacts with
pups, their pups retrieval and return in the nest happened later in
comparison with Wistar rats. This peculiarities of maternal behavior
may be consequence of typical for WAG/Rij rats increased anxiety and
emotional reactivity on novel situation as well as decreased maternal
care. Together WAG/Rij rats built nest more often (55% of observations)
in comparison with Wistar rats (23% of observations). After experiments
WAG/Rij rats had the nests with higher walls. Also Wag/Rij rats showed
lasting behavioral reactions more often (66% of observations) than
Wistar rats (27% of observations).
148

Thus WAG/Rij mothers exhibited delay of maternal behavior after


disturbance in their nests, increased nest building and displaced
activity as anomalous prolongations of some behavior reaction.
Changed maternal behavior can influence on the development of
nervous system and behavior in offspring of WAG/Rij rats.
This work was supported by grant of the RFBI number 13-04-00741


..
.
.., ,
eayumatov@mail.ru

. , ,
. ,
,


. . . , (1995),
,


.
,
.. , (1951); .
, (1952); .. , (1969); .. , (1995); ..
, (2010),
.

:
,
;
,
. ,
. ,

,
, ,
.
.
, ,
, ,
.
, . ,
(2001),

:
,
, ,
,
,
, .
149

,
.
, ,
, ,
.
.

,

,

(.. , 2010, 2011, 2012).

- (..
, .. , .. , .. , 2012, 2013).
,
.


, ,
,
( ).

,

,
(.. , 2012).

PSYCHOPHYSIOLOGY THE VISIBLE AND HIDDEN PARTS


OF "ICEBERG"
Yumatov E.A.
Sechenov First Moscow State Medical University. Russia.
eayumatov@mail.ru
The origin of a human subjective state is discussed. The brain
activity has two facets: visible, characterized by registered
neurophysiologic parameters, and hidden or spiritual, manifesting in
human subjective perception of oneself and the world around him/her. No
doubt, these to facets are interrelated. There are no even
hypothetical, logical concepts in science that explain the origins of
the subjective in neurophysiological processes.
There is a huge gap up between modern knowledge about brain
neurophysiology and understanding of its mental functions. This is due
to the fact the brain was studied with the morphological, physical and
chemical methods based on the knowledge, phenomena and laws discovered
in the investigations of the abiocoen.
150

A living organism and a brain in particular may be the place for


physical phenomena and processes that are impossible in the abiocoen.
This thesis has principal importance for understanding the essence of
the subjective in the brain activity.
For the first time it is showed that, the human subjective states
can be registered remotely and objectively. The author establishes the
existence of a "psychogenic field", reflecting the human brain
subjective state. New unknown phenomena and properties of the brain are
discovered. The author is showed the remote influence of the human
subjective state on the physical and chemical
properties of the
blood.
The author expresses the concept of specific physical phenomena in
the brain that can not exist in the abiocoen. The schematic diagram of
reproduction of subjective feelings in brain activity at which neural,
molecular structures of a brain at the same time are "generator" of
specific field processes and "screen" which this field (a brain selfinduction)
influence
is
submitted.
The
interrelation
of
neurophysiologic and subjective processes in the system organization of
goal-seeking behavior is described and a paradigm presuming the
existence of physical phenomena unique for the living brain and brain
fields, and their role in the origin of a subjective state is
suggested.

.. 1, .. 2, .. 1, .. 1,
.. 1, .. 1, .. 1, .. 1, .. 1,
.. 1, .. 1
1


. .. ..
, 117997, . - 16/10
2
(
), 117198, . -, 8
elena-yagudaeva@yandex.ru

-
. A, C,
Y, W135 ,

- ,
.
(N.meningitidis, N.gonorrhoeae,
H.influenzae, St.pneumonia .) - IgA1 ,
.
IgA1
151

, , ,
.
, IgA1

, .

IgA1

.
,
.

IgA1
IgA1
.
IgA1

(1:2 560 1:20 000 ).



,
Balb/C .
, 40 - 60%
.
IgA1
(- S.typhi,
)
.
11-04-00895-
2013 .

NEW APPROACHES TO CREATING OF POLYVALENT VACCINE


AGAINST MENINGOCOCCUS
E.Yu. Yagudaeva1, A.P. Alliluev2, E.A. Gordeeva1, L.S. Zhigis1, A.A.
Zinchenko1, V.S. Zueva1,
O.V. Kotelnikova1, T.D. Melikhova1, E.A. Nokel1, O.V. Serova1,
L.D. Rumsh1
1

ShemyakinOvchinnikov Institute of Bioorganic Chemistry, Russian


Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia
2
Medical Faculty, Russian University of Peoples Friendship, ul.
Miklukho-Maklaya 8, Moscow, 117198, Russia
elena-yagudaeva@yandex.ru
The vaccine creation against meningococcus serogroup B is a very
vital task due to its lack in practice of world healthcare. Vaccines
against meningococcus serogroup A, C, Y, W135 are produced on the base
of capsular polysaccharides, but polysaccharide of meningococcus
152

serogroup B can not be used as a vaccine because of its special


properties associated with molecular structure.
Agents, causing a variety of infections (N.meningitidis,
N.gonorrhoeae, H.influenzae, St.pneumonia and etc.), secrete the enzyme
- IgA1 protease, which is one of their pathogenic factors. High
structural homology of these IgA1 proteases allows to suggest that
vaccine, constructed on the base of this enzyme, will be effective
against all of mentioned above infections.
The activity of these drugs was evaluated the protection level
against meningococcus serogroup A, B and C using Balb/-line mice
infection model with live virulent strains of these microorganisms.
In this work by methods of gene engineering the constructs of
recombinant DNA plasmid were created, as well as strains producing
enzymatically active and mutant forms of recombinant IgA1 protease of
meningococcus serogroup B in the form of inclusion bodies. The methods
for obtaining, isolation and purification of recombinant proteins were
developed.
Comparative study of photolytic activity of IgA1-protease in
active and mutant form showed the high specificity of obtained samples
by detection IgA1 in serum from healthy human and patients with
bacterial meningitides by ELISA assay.
High immunogenicity of IgA1-protease preparations and its
capability to induce formation of immune memory were found by
evaluating the titer of specific antibodies in mice serum after single
and double immunization with these preparations (1:2560 and 1:20000
respectively).
Protective activity of obtained preparations was assessed by the
protection level against meningococcus serogroup A, B and C using
Balb/-line mice infection model with live virulent strains of these
microorganisms. Depending on the serogroup protection level was 40-60%
as compared with this value for control group of non-immunized mice.
Mice immunization with IgA1-protease preparations did not prevent
the formation of immunity against foreign antigens (Vi-antigen S.typhi,
sheep red blood cells) and not increase the growth of grafted animal
cervix carcinoma.
This work was financially supported by RFBR 11-04-00895- and by
Program RAS Fundamental sciences for medicine 2013.

-


.., ..
... , ,
dmitry@shamenkov.com
.

(
)

153

- (),
, ..,

.
. ,

, ,
,

,
,

().

,

.

, .

, ,
, .

,

.

, ,
,
,

Google Analytics.
. TheHealthBook.ru
, 3500 ,
85% - .

( 52 500 ),
TheHealthBook.ru,

" ",
-
.


. .
.


,
.

154

Development of a health management model based on the theory of


functional systems by P.K.Anokhin
D. Shamenkov, I. Kaledin
Normal Human Physiology Scientific Centre n.a. P.Anokhin at Russian
Academy of Medical Sciences , Moscow, Russia,
dmitry@shamenkov.com

Due to widespread acceptance of information and communication


technologies there was a growing interest in informational aspect of
public health in recent years [N.A. Christakis, 2007, 2010, 2011, 2012;
A.Pentland, 2004, 2005, 2010, 2011, 2012; D. Kraft, 2012].
Fast spread of technical devices and communication means distracts
people from controlling their personal health parameters and reduces
their responsibility in maintaining personal well-being. At the same
time, constant increase in speed and density of information flow along
with recent social and political changes, and environmental problems
keep modern humanity under constant stress, causing noninfectious,
primarily psychosomatic epidemic [Lim SS, 2012].
Present study is based upon a prioritized theory of functional
systems, suggested by Pyotr Anokhin [P.K.Anokhin, 1968]
According to the concept of "information equivalent of reality"
introduced by Anokhin, there is a constant information flow in
functional systems. In elaboration of these understanding it was found
that information originates as ratio of deviated value of adaptive
result to its life-optimum level [Sudakov, K.V., 1999].
Functional systems of living organisms are hierarchically
structured [Sudakov, K.V.,]. According to this principle, higher level
functional systems program lower level functional systems activity on
atomic, genetic, molecular, homeostatic and organismic levels. These
functional systems are subordinated to systems of population,
psychical, social and higher levels.
Based on assumptions of the theory of functional systems, personal
health is largely determined by higher level systems.
Since the advent of modern information and communication
technologies, such as the Internet and search systems, these
communication channels has opened up a possibility for users to
exchange information on information equivalent of needs and information
equivalents of action results.
It is the purpose of this article to explore the possibility of
using information and communication technologies (social networks and
modern online education technology) for evaluation and management of
systemic personal health criteria.
For purposes of this research we created a special computer model
of system classification of users with identical diseases who have
similar living conditions, behavioral pattern and social activities.
Individuals tend to organize in functional systems based on their
health support needs. This socially organized functional system forms a
generalized socially important information acceptor of action result
155

based on social network along with personal representation of every


single user. This system organization is designed to acquire knowledge
about personal health and health of similar users. Similar diseases
generate similar motivation in users aimed at their elimination. This
enables them to interact on close action programs and collectively
update the generalized acceptor apparatus of action result and their
individual acceptors of action result.
The model includes participation of medical professionals and
psychologists who provide necessary recommendations to other system
users.
User activity within the system satisfies their need for
information and finding similar users, resulting in generation of
information signals in the form of positive emotions.
The ultimate result of model activity is social health of the
population, organized in the suggested functional system.
Principles of development of a health management model based on
the theory of functional systems:
Social system of health management is structured according
to functional systems hierarchy.
Social health management functional system with generalized
information acceptor of action result is created with the help of
effective interaction between system users based on personal
motivations.
Feedback effect of the suggested model, mainly generalized
information acceptor increases the effectiveness of functional
system on the account of information exchange between users.
Methods. In order to examine the outcome of computer model of
social health management system activity (its importance and frequency
of use) we used graphical analysis of structure and dynamics of social
network, qualitative and quantitative evaluation of information flow
nodes, standard demographic and geographic analysis of users base
structure with the help of Google Analytics.
Results obtained. Over the course of one year since establishing
the TheHealthBook.ru website, a sustainable community of 3000 users has
formed, 85% of which has become its regular visitors. This shows high
motivation of users and high value of information acquired followed by
positive emotional reinforcement. This project gathered a numerous
audience of like-minded regular returning visitors (over 52,500 people,
60% regular users) of the website with educational materials on the
system. Most users demonstrate practical value of systematic contacts
for their well-being.
Conclusions. We proved that modern information, communication and
education technologies can be applied based on theory of functional
systems by P.Anokhin for development of effective information computer
model for population health maintenance.

156


.. 11
.. 88
.. 13, 25
.. 145
.. 73
.. 127
.. 93
.. 15
.. 151
.. 73
.. 53, 76, 125, 132
.. 18
.. 21
.. 39
.. 42
.. 31
.. 23
.. 132
.. 39
.. 116
.. 88
.. 108, 124
.. 25
.. 28
.. 140
.. 23
.. 73
.. 73
.. 31
.. 42
.. 42
.. 31
.. 145
.. 47
.. 151
.. 73
.. 33
.. 35, 37, 41, 145
.. 39
.. 41, 42
.. 44
.. 18, 47
.. 49
.. 35
.. 21
.. 73
.. 53, 76
.. 49
.. 39
.. 151
.. 55, 103
.. 13, 25, 28
.. 42
.. 57
.. 151
.. 59

.. 88
.. 151
.. 49
.. 31
.. 79
.. 28
.. 81
.. 31
.. 61
.. 31
.. 64
.. 35
.. 47
.. 18
.. 153
.. 66
.. 69, 140
.. 88
.. 39
.. 106
.. 106
.. 108. 124
.. 106
.. 72
.. 132
.. 73
.. 73
.. 76
.. 79, 81
.. 84
.. 73
.. 151
.. 64
.. 86
.. 120
.. 103
.. 35
.. 21
.. 88
.. 90
.. 59
.. 103
.. 93
.. 95
. 23
.. 151
.. 15
.. 49
.. 97
.. 88, 100
.. 55, 103
.. 49
.. 106
.. 127
.. 42
.. 108, 124

157

.. 108, 124
.. 151
.. 93
.. 15
.. 111, 135
.. 95, 113
.. 49
.. 145
.. 116
.. 122
.. 88
.. 118
.. 120
.. 97, 151
.. 35
.. 47
.. 122
.. 151
.. 103
.. 116
.. 49
.. 88
.. 108, 124
.. 125
.. 37, 88, 145
.. 3
.. 127
.. 88

158

. 129
.. 132
.. 111, 135
.. 137
.. 49, 137
.. 86
.. 33
.. 108, 124
.. 42
.. 140
.. 93
.. 147
.. 142
.. 118
.. 153
.. 142
.. 35, 37, 88, 145
.. 147
.. 21
.. 149
.. 151
Bokhan N.A. 42
Davydov Dmitry M. 52
Kucheryanu V. G. 41
Magdalena Koscik 52
Morozova-Roche L.A. 41, 105
Ra Czabak-Garbacz 52
Sewell R.D.E. 37, 41



127473, , 3- ., 9
. (495) 684-43-33
(495) 684-43-33
-mail: moffice@materiamedica.ru
www.materiamedica.ru
www.anaferon.ru

-
. 20
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, 2006 2007
( 96 20 2006 12 22 2007 )

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Iinstitute for Antiviral Research (USA),
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RESEARCH AND MANUFACTURING COMPANY MATERIA MEDICA HOLDING


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