Hirano Bodies Sayfa 1 / 3

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Hirano Bodies
updated 13/5/02
Hirano bodies were first described in 1965 (Hirano, 1965). They are intracellular, paracrystalline, eosinophilic structures often occurring
as rod shapes in the neurons of individuals with a number of neuro-degenerative diseases including Alzheimer's and some forms of
Creutzfeldt-Jacob disease (Cartier et al, 1985). Although Hirano bodies are most often encountered in neurons of the central nervous
system, particularly the Somer's section in Alzheimer's, they have been reported in glial cells, in peripheral nerve axons (Laas & Hagel,
1994), and in extraocular muscles of eyes (Tomonaga, 1983), and rarley even in skeletal muscle (Fernadez et al, 1999). Hirano bodies
are observed increasingly as a function of age without obvious underlying neurodegeration (Ogata et al, 1972; Gibson & Tomlinson,
1977).

Figure 1

From Maciver & Harrington, 1995. Hirano Bodies in the CA1 area of hippocampal
formation in Alzheimer's disease labelled with anti-ADF serum. Hirano bodies are restricted
to this area and are found in the vicinity of pyramidal cells which are often affected by
cytoplasmic granulovacoular degeneration (CGD) (A, arrows). GVD can be seen as several
haemotoxalin-stained granules, each surrounded by a negatively stained halo (also seen at
higher magnification in B and C). GVD was not stained with anti-ADF. The shapes of the
Hirano bodies vary from small ovoid structures to longer , narrow bodies (5-10µm in width;
10-30µm in length). The majority are stained evenly throughout (A, B) although there are
often bodies in which the labelling does not appear to penetrate the body, giving an
appearance of the antibody reacting with epitopes on the surface of the Hirano body
(arrowhead, A). Two distinct staining patterns are seen in C: one body on the left is surface
labelled, whereas that on the right is labelled intensely throughout. Scale bars: A, 40µm; B,C,
10µm.

Protein Function References

α-actinin An actin-filament bundling protein Galloway et al, 1987a
A structural component of almost all Goldman 1983; Galloway et al,
actin
eukaryotic cells 1987a
ADF/cofilin Actin-binding severing proteins. Maciver & Harrington, 1995
The principle component of
β-APP (C-terminal) Munoz et al, 1993
Alzheimer's tangles
FAC1 Normally a nucealar protein Jordan-Sciutto et al, 1998
HCNP A brain signalling molecule Mitake et al, 1995
Hsp27 A chaperonin that also binds actin Renkawek et al, 1994
Inducible nitric oxide synthase, a
iNOS signal generating enzyme involved in Lee et al, 1999
smooth muscle contraction
Microtubule-associated/bundling
MAP1 Peterson et al, 1988
protein
Microtubule-associated/bundling
MAP2 Peterson et al, 1988
protein
Neurofilament proteins An intermediate filament protein Schmidt et al, 1989
Microtubule-associated/bundling
Tau Galloway et al, 1987b
protein
An actin binding protein that regulates Galloway et al, 1987a; Peterson
Tropomyosin
interactions with myosin. et al, 1988
A component of the focal adhesion
Vinculin Galloway et al, 1987a
complex that also binds actin.

Table 1 Proteins constituents of Hirano bodies

Actin in Hirano bodies

Actin was discovered to be a component of Hirano bodies about 20 years after their discovery (Goldman, 1983; Galloway et al, 1987a).
The nature of the actin in Hirano bodies is generally supposed to be filamentous, perhaps explaining the filaments seen in regular arrays
within the bodies, as Hirano bodies stain with phalloidin (a specific stain for F-actin) (Galloway et al, 1987a). More recently (Rossiter et
al, 2000) it has been reported that a proportion of the actin in Hirano bodies at least exists as a fragmented form called "fractin" after it
has been attacked by the apoptosis protease caspase which cleaves actin at to form two peptides and revealing a peptide (YELPD) against
which antibodies were made. Hirano bodies are different from many other actin structures in that they bind both ADF/cofilin and

http://www.bms.ed.ac.uk/research/others/smaciver/Cyto-Topics/hirano_bodies.htm 22.10.2010
Hirano Bodies Sayfa 2 / 3

phalloidin, normally mutually exclusive actin-binding agents.

Figure 2
The Structure of Hirano bodies
Depending on the section at the E.M. level, Hirano bodies appear to be sets of parallel filaments with equally distanced nodes or
associated with feathery projections (Schochet & McCormick, 1972 ; Izumiyama et al, 1991). A representation of the simplest
interpretation of the structure is given in figure 2 although it it recognised that this is very much oversimplified. This basic unit is repeated
within the Hirano body. At the level of the light microscope, the structures seem to be dense as antibody complexes seem incapable of
penetrating the structures fully (Maciver & Harrington, 1995; Jordan-Sciutto et al, 1998)

Lewy Bodies
Superficially at least Hirano bodies are similar to Lewy bodies. One difference is that Lewy bodies contain ubiquitin whereas Hirano
bodies do not (Maciver & Harrington, 1995).
References:-

Cartier, L, Galvez, S. & Gajdusek, D.C. (1985) Familial clustering of the ataxic form of Creutzfeldt-Jacob disease with Hirano bodies.
J.Neurol.Neurosurg.Psychiatry 48(3), 234-238.

Fernandez, R., Fernandez, J. M., Cervera, C., Teijeira, S., Teijeira, A., Dominquez, C. & Navarro, C. (1999) Adult glycogenosis II with paracrystalline mitochondrial
inclusions and Hirano bodies in skeletal muscle. Neuromuscular Disorders. 9, 136-143.

Galloway, P. G., Perry, G. & Gambetti, P. (1987a) Hirano body filaments contain actin and actin-associated proteins. J.Neuropathol.Exp.Neurol. 46, 185-199.

Galloawy, P.G., Perry, G., Kosik, K.S., & Gambetti, P.(1987b) Hirano bodies contain tau protein. Brain Res. 403, 337-340.

Gibson, P. H. & Tomlinson, B. E. (1977) Numbers of Hirano bodies in the hippocampus of normal and demented people with Alzheimer's disease. J.Neurol.Sci. 33,
199-206.

Goldman, J.E. (1983) The association of actin with Hirano bodies. J.Neuropathol.Exp.Neurol. 42, 146-152.

Hirano, A. (1965) Pathology of amyotrophic lateral sclerosis. In: Slow latent and temperate virus infections, NINDB monograph No.2 pp23-37. Gajdosek & Gibbs
eds. Bethesda. National Inst.Health.

Hirano, A. (1994) Hirano bodies and related neuronal inclusions. Neuropath.Appl.Neurobiol. 20, 3-11.

Izumiyama, N., Ohtsubo, K., Tachikawa, T. & Nakamura, H. (1991) Elucidation of three-dimentional ultrastructure of Hirano bodies by the quick-frozen, deep-etch
and replica method. Acta Neuropathol. 81, 248-254.

Jordan-Sciutto, K., Dragich, J., Walcott, D. Bowser, R. (1998) The presence of FAC1 protein in Hirano bodies. Neuropath.Appl.Neurobiol. 24, 359-366.

Laas, R., Hagel, C. (1994). Hirano bodies and chronic alcoholism. Neuropathol. Appl.Neurobiol. 20, 12-21.

Lee, S.C., Zhao, M.L., Hirano, A. & Dickson, D.W. (1999). Inducible nitric oxide synthase immunoreactivity in the Alzheimer disease hippocampus: association
with Hirano bodies, neurofibrillary tangle, and senile plaques. J.Neuropathol.Exp.Neurol. 11, 1163-1169.

Maciver, S. K. & Harrington, C. R. (1995) Two actin-binding proteins, actin depolymerizing factor and cofilin, are associated with hirano bodies. Neuroreport. 6,
1985-1988.

Maselli, A. G., Davis, R., Furukawa, R. & Fechheimer, M. (2002) Formation of Hirano bodies in Dictyostelium and mammalian cells induces by expression of a
modified form of an actin-crosslinking protein. J.Cell Sci. 115, 1939-1952.

Mitake, S., Ojika, K., Katada, E., Otsuka, Y., Matsukawa, N. & Fujimori, O. (1995) Accumulation of hippocampal cholinergic neurostimulating peptide (HCNP)-
related components in Hirano bodies. Neuropath.Appl.Neurobiol. 21, 35-40.

Peterson, C., Kress, Y., Vallee, R. & Goldman, J. E. (1988) High molecular weight microtubule-associated proteins bind to actin lattices (Hirano bodies). Acta
Neuropathol. 77, 168-174.

Renkawek, K., Bosman, G. J. C. & de Jong, W. W. (1994) Expression of small heat-shock protein hsp27 in reactive gliosis in Alzheimer disease and other types of
demetia. Acta Neuropathol. 87, 511-519.

Rossiter, J. P., Anderson, L. L., Yang, F. & Cole, G. M. (2000) Caspase-cleaved actin (fractin) immunolabelling of Hirano bodies., Neuropathol. Appl.Neurobiol. 26,
342-346.

Schmidt, M. L., Lee, V. M.-Y. & Trojanowski, J. Q. (1989) Analysis of epitopes shared by Hirano bodies and neurofilament proteins in normal and Alzheimer's
disease hippocampus. Lab.Invest. 60, 513-522.

Schochet, S. S. & McCormick, W. F. (1972) Ultrastructure of Hirano bodies. Acta Neuropathol. 21, 50-60.

http://www.bms.ed.ac.uk/research/others/smaciver/Cyto-Topics/hirano_bodies.htm 22.10.2010
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Tomanaga, M. (1983) Hirano body in extraocular muscle. Acta Neuropathol. 60, 309-313.

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