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Argyrophilic ubiquitinated cytoplasmic inclusions of Leu-7-positive glial cells in olivopontocerebellar atrophy (multiple system atrophy)

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Summary

We described cytoplasmic inclusions in glial cells in 18 patients with olivopontocerebellar atrophy (OPCA) (multiple system atrophy, MSA). These glial inclusions showed intense argyrophilia with modified Bielschowsky's and Bodian's silver impregnation techniques, and were observed in the pons, cerebellar white matter, midbrain, medulla oblongata and basal ganglia, as well as cerebral white matter and spinal cord. None of the 54 control cases had glial argyrophilic inclusions. Immunohistochemically, these inclusions were intensely labeled by anti-ubiquitin antibody. Some of them reacted with an antibody to Rosenthal fiber (RF) protein. The cytoplasm of ubiquitinated inclusion-bearing glial cells was immunostained by anti-Leu-7 antibody, but not by anti-GFAP antibody. Ultrastructurally, the glial inclusions were composed primarily of approximately 24- to 40-nm fibrils, which were coated with osmiophilic granular material along their length in longitudinal section. These fibrils appeared as annuli in cross section. Often, a central granule approximately 5 nm in diameter was seen in the lucent lumen of a cross-sectioned fibril. The granule-coated fibrils were not seen in the glial filament-containing astrocytes. Electron microscopic examination of silver-impregnated specimens revealed that the granule-coated fibrils had strong affinity for silver. Immunoelectron microscopy using the indirect immunoperoxidase techniques with antibodies to ubiquitin and RF protein revealed that the electron-dense reaction products respective to both were located on constituents of glial inclusions. Our observation that Leu-7-positive glial cells, mainly oligodendroglial cells, had argyrophilic ubiquitinated inclusions may be of significance for the evaluation of the pathology of OPCA(MSA).

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References

  1. Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101:1371–1378

    Google Scholar 

  2. Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15:13–26

    Google Scholar 

  3. Budka H (1990) Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS). Acta Neuropathol 79:611–619

    Google Scholar 

  4. Dickson DW, Kress Y, Crowe A, Yen S-H (1985) Monoclonal antibodies to Alzheimer neurofibrillary tangles. 2. Demonstration of a common antigenic determinant between ANT and neurofibrillary degeneration in progressive supranuclear palsy. Am J Pathol 120:292–303

    Google Scholar 

  5. Essick CR (1912) The development of the nuclei pontis and the nucleus arcuatus in man. Am J Anat 13:25–54

    Google Scholar 

  6. Horoupian DS, Dickson DW (1991) Striatonigral degeneration, olivopontocerebellar atrophy and “atypical” Pick disease. Acta Neuropathol 81:287–295

    Google Scholar 

  7. Iwaki T, Kume-Iwaki A, Liem RKH, Goldman JE (1989) αB-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. Cell 57:71–78

    Google Scholar 

  8. Iwaki T, Kume-Iwaki A, Goldman JE (1990) Cellular distribution of αB-crystallin in non-lenticular tissues. J Histochem Cytochem 38:31–39

    Google Scholar 

  9. Kato S, Nakamura H (1990) Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol 79:584–594

    Google Scholar 

  10. Kato S, Nakamura H (1990) Presence of two different fibril subtypes in the Pick body: an immunoelectron microscopic study. Acta Neuropathol 81:125–129

    Google Scholar 

  11. Kato S, Nakamura H, Otomo E (1989) Reappraisal of neurofibrillary tangles: immunohistochemical, ultrastructural, and immunoelectron microscopical studies. Acta Neuropathol 77:258–266

    Google Scholar 

  12. Lowe J, Blanchard A, Morrell K, Lennox G, Reynolds L, Billett M, Landon M, Mayer RJ (1988) Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibers in cerebellar astrocytomas, cytoplasmic bodies in muscle, and Mallory bodies in alcoholic liver disease. J Pathol 155:9–15

    Google Scholar 

  13. McGarry RC, Helfand SL, Quarles RH, Roder JC (1983) Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1. Nature 306:376–378

    Google Scholar 

  14. Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science 235:1641–1644

    Google Scholar 

  15. Motoi M, Yoshino T, Hayashi K, Nose S, Horie Y, Ogawa K (1985) Immunohistochemical studies on human brain tumors using anti-Leu-7 monoclonal antibody in paraffin-embedded specimens. Acta Neuropathol (Berl) 66:75–77

    Google Scholar 

  16. Nakazato Y, Sasaki A, Hirato J, Ishida Y (1987) Monoclonal antibodies which recognize phosphorylated and nonphosphorylated epitopes of neurofilament protein. Biomed Res 8:369–376

    Google Scholar 

  17. Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1990) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 49:521–530

    Google Scholar 

  18. Papasozomenos SC, Binder LI (1987) Phosphorylation determines two distinct species of tau in the central nervous system. Cell Motil Cytoskel 8:210–226

    Google Scholar 

  19. Papasozomenos SC (1989) Tau protein immunoreactivity in dementia of the Alzheimer type. I. Morphology, evolution, distribution, and pathogenetic implications. Lab Invest 60:123–137

    Google Scholar 

  20. Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100

    Google Scholar 

  21. Yamamoto T, Hirano A (1986) A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer's neurofibrillary tangles. Neuropathol Appl Neurobiol 12:3–9

    Google Scholar 

  22. Yen S-H, Crowe A, Dickson DW (1985) Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides. Am J Pathol 120:282–291

    Google Scholar 

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Supported in part by a grant from the Amyotrophic Lateral Sclerosis Association. Part of this study was presented at the 11th International Congress of Neuropathology in Kyoto, Japan, September 1990.

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Kato, S., Nakamura, H., Hirano, A. et al. Argyrophilic ubiquitinated cytoplasmic inclusions of Leu-7-positive glial cells in olivopontocerebellar atrophy (multiple system atrophy). Acta Neuropathol 82, 488–493 (1991). https://doi.org/10.1007/BF00293383

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  • DOI: https://doi.org/10.1007/BF00293383

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