Summary
Neuronal alterations in five cases of multiple system atrophy (MSA) were investigated histologically, immunocytochemically and ultrastructurally. Argentophilic neuronal cytoplasmic inclusions (NCIs) were observed in all cases. They were distributed, in order of decreasing frequency, in the pontine nucleus, striatum, subiculum, amygdala, hippocampus, dentate fascia, substantia nigra and inferior olivary nucleus. Anti-ubiquitin antibodies visualized many thickened neurites in the degenerating gray matter as well as NCIs. Some NCIs were also recognized by anti-phosphorylated neurofilament antibodies. Ultrastructurally, NCIs consisted of a meshwork of granule-associated filaments, the diameter ranging from 18 to 28 nm, that were mixed with neurofilaments. The granule-associated filaments were also present in the axoplasm of myelinated fibers. Our studies demonstrate widespread distribution of NCIs in the central nervous system of MSA. The same pathological process that forms the granule-associated filaments in axons may also be responsible for the formation of ubiquitin-positive thickened neurites. These axonal alterations, as well as neuronal perikaryal changes, may play an important role in the impaired neuronal function in MSA.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Haas AL, Bright PM (1985) The immunocytochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J Biol Chem 260:12464–12473
Horoupian DS, Dickson DW (1991) Striatonigral degeneration, olivopontocerebellar atrophy and “atypical” Pick disease. Acta Neuropathol 81:287–295
Ihara Y (1988) Massive somatodndritic sprouting of cortical neurons in Alzheimer's disease. Brain Res 459:138–144
Ihara Y, Nukina N, Sugita H, Toyokura Y (1981) Staining of Alzheimer's neurofibrillary tangles with antiserum against 200K component of neurofilament. Proc Jpn Acad 57B:152–156
Ihara Y, Carmela A, Selkoe DJ (1983) Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain protein. Nature 304:727–730
Kato S, Nakamura H (1990) Cytoplasmic argyrophilic inclusions in neurons in pontine nuclei in patients with olivopontocerebellar atrophy: immunocytochemical and ultrastructural studies. Acta Neuropathol 79:584–594
Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y (1988) Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. Acta Neuropathol (Berl) 75:345–353
Leigh PN, Swash M (1991) Cytoskeletal pathology in motor neuron disease. Adv Neurol 56:115–124
Leigh PN, Probst A, Dale GE, Power DP, Brion J-P, Donson A, Anderton BH (1989) New aspects of the pathology of neurodegenerative disorders as revealed by ubiquitin antibodies. Acta Neuropathol 79:61–72
Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's diseae. Science 235:1641–1644
Murayama S, Ookawa Y, Mori H, Nakano I, Ihara Y, Kuzuhara S, Tomonaga M (1989) Immunocytochemical and ultrastructural study of Lewy body-like hyaline inclusions in familial amyotrophic lateral sclerosis. Acta Neuropathol 78:143–152
Murayama S, Mori H, Ihara Y, Bouldin TW, Suzuki K, Tomonaga M (1990) Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. Ann Neurol 27:137–148
Murayama S, Arima K, Satoh J, Oda M, Nakazato Y, Inose T (1992) Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 2. Oligodendroglial cytoplasmic inclusions. Acta Neuropathol (in press)
Murayama S, Bouldin TW, Suzuki K (1992) Immunocytochemical and ultrastructural studies of upper motor neurons in amyotrophic lateral sclerosis. Acta Neuropathol (in press)
Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1990) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 49:521–530
Nukina N, Ihara Y (1983) Immunocytochemical study on senile plaques in Alzheimer's disease. I. Preparation of anti-microtubule-associated proteins (MAPS) antiserum and its specificity. Proc Jpn Acad 59B:284–287
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
Probst A, Langui D, Lautenschlager C, Ulrich J, Brion JP, Anderton BH (1988) Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles. Acta Neuropathol 77:61–68
Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated and non-phosphorylated forms of neurofilament in situ. Proc Natl Acad Sci USA 80:6126–6130
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arima, K., Murayama, S., Mukoyama, M. et al. Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. Acta Neuropathol 83, 453–460 (1992). https://doi.org/10.1007/BF00310020
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00310020