Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy

Murayama, Shigeo; Arima, Kunimasa; Nakazato, Yoichi; Satoh, Jun‐ichi; Oda, Masaya; Inose, Tomoko

doi:10.1007/bf00427212

Cited by 70 publications

(54 citation statements)

References 23 publications

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“…GCI found in MSA are consistently stained with Bielschowski and Gallyas and strongly react with antibodies to ubiquitin [39]. They have also been reported to react with antibodies to alpha-and betatubulin [33,[41][42][43], alpha-, beta-crystallin [44], microtubule-associated protein MAP5 [9,45], MAP1 [46] and MAP2 [47]. However, variable immunolabeling of GCI was obtained with antitau antibodies [40-42, 44, 46, 47].…”

Section: Discussionmentioning

confidence: 99%

Primary Progressive Aphasia with Glial Cytoplasmic Inclusions

Molina

Probst²,

Villanueva

et al. 1998

Eur Neurol

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We report a 80-year-old woman who suffered from primary progressive aphasia for 3 years. Cranial CT and MRI studies showed moderate cerebral atrophy, more marked in the left frontal and temporal lobes, and SPECT brain scans revealed marked hypometabolism in the left frontal and temporal lobes. Neuropathologic examination of a temporal lobe biopsy demonstrated Gallyas-positive intracytoplasmic inclusions looking like fibrillary tangles and of Gallyas-positive cell processes, probably from glial cells. Glial intracytoplasmic inclusions were immunolabelled with antibodies to ubiquitin and with phosphorylion-dependent antitau antibodies, indicating the presence of hyperphosphorylated tau in the inclusions. There was only mild pathology of cortical neurons consisting in rare perikarya diffusely stained with antitau antibodies. There were no senile plaques, neurofibrillary tangles, ‘achromatic’ neurons, ballooned cells, Pick or Lewy bodies, nor microvacuoles or spongiform changes of the neuropil. The glial intracytoplasmic inclusions found in this case were similar to those found in multiple system atrophy, and differ from the cortical changes hitherto reported in primary progressive aphasia.

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Section: Discussionmentioning

confidence: 99%

Primary Progressive Aphasia with Glial Cytoplasmic Inclusions

Molina

Probst²,

Villanueva

et al. 1998

Eur Neurol

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“…For example, fibrillary aggregates in OLGs known as glial cytoplasmic inclusions (GCIs) are hallmark lesions of multiple system atrophy (MSA), and GCIs are composed of ␣-synuclein as well as tau but to a lesser extent (Murayama et al, 1992;Tu et al, 1998) (for review, see Richter-Landsberg, 2000). Other filamentous OLG inclusions known as coiled bodies are primarily composed of hyperphosphorylated tau (Chin and Goldman, 1996;Dickson et al, 1996;Forman et al, 2002), and these inclusions are characteristic of several frontotemporal dementias (FTDs) such as sporadic progressive supranuclear palsy (PSP), Pick's disease, and corticobasal degeneration (CBD), as well as hereditary FTD with parkinsonism linked to chromosome 17 (FTDP-17) (for review, see Komori, 1999;Forman et al, 2000;Richter-Landsberg, 2000).…”

Section: Introductionmentioning

confidence: 99%

Axonal Degeneration Induced by Targeted Expression of Mutant Human Tau in Oligodendrocytes of Transgenic Mice That Model Glial Tauopathies

Higuchi

Zhang²,

Forman³

et al. 2005

J. Neurosci.

111

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Abundant filamentous tau inclusions in oligodendrocytes (OLGs) are hallmarks of neurodegenerative tauopathies, including sporadic corticobasal degeneration and hereditary frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). However, mechanisms of neurodegeneration in these tauopathies are unclear in part because of the lack of animal models for experimental analysis. We address this by generating transgenic (Tg) mice expressing human tau exclusively in OLGs using the 2Ј,3Ј-cyclic nucleotide 3Ј-phosphodiesterase promoter. Filamentous OLG tau inclusions developed in these Tg mice as a result of human tau expression in OLGs, especially those expressing the FTDP-17 human P301L mutant tau. Notably, structural disruption of myelin and axons preceded the emergence of thioflavin-S positive tau inclusions in OLGs, but impairments in axonal transport occurred even earlier, whereas motor deficits developed subsequently, especially in Tg mice with the highest tau expression levels. These data suggest that the accumulation of tau in OLG cause neurodegeneration, and we infer they do so by disrupting axonal transport. We suggest that similar defects may also occur in sporadic and hereditary human tauopathies with OLG tau pathologies.

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“…Glial fibrillary tangles (GFTs) or "coiled bodies" are observed specifically in Pick's disease, PSP, and CBD, and glial cytoplasmic inclusions (GCIs) in oligodendroglia are the histological hallmarks of multiple system atrophy (MSA). GCIs stain consistently and intensely with antibodies against ubiquitin, the small heat shock protein ␣B-crystallin, and ␣-synuclein and less intensely with antibodies against ␣-and ␤-tubulin; variable reports indicate that they are tau-positive (Murayama et al, 1992;Chin and Goldman, 1996;Lantos, 1998;Tu et al, 1998;Komori, 1999). They appear as loosely packed filaments.…”

Section: Introductionmentioning

confidence: 99%

Proteolytic Stress Causes Heat Shock Protein Induction, Tau Ubiquitination, and the Recruitment of Ubiquitin to Tau-Positive Aggregates in Oligodendrocytes in Culture

Goldbaum¹,

Richter‐Landsberg²

2004

J. Neurosci.

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Molecular chaperones and the ubiquitin-proteasome system are participants in the defense against unfolded proteins and provide an effective protein quality control system that is essential for cellular functions and survival. Ubiquitinated tau-positive inclusion bodies containing the small heat shock protein ␣B-crystallin in oligodendrocytes are consistent features of a variety of neurodegenerative diseases, and defects in the proteasome system might contribute to the aggregation process. Oligodendrocytes, the myelin-forming cells of the CNS, are specifically sensitive to stress situations. Here we can show that in cultured rat brain oligodendrocytes proteasomal inhibition by MG-132 or lactacystin caused apoptotic cell death and the induction of heat shock proteins in a time-and concentrationdependent manner. Specifically, ␣B-crystallin was upregulated, and ubiquitinated proteins accumulated. After incubation with MG-132 the tau was dephosphorylated, which enhanced its microtubule-binding capacity. Proteasomal inhibition led to ubiquitination of tau and its association with ␣B-crystallin and to the occurrence of thioflavine S-positive aggregates in the oligodendroglial cytoplasm. These aggregates were positive for tau and also contained ubiquitin and ␣B-crystallin; hence they resembled the glial cytoplasmic inclusions observed in white matter disease and frontotemporal dementias with parkinsonism linked to chromosome 17 (FTDP-17). In summary, the data underscore the specific sensitivity of oligodendrocytes to stress situations and point to a causal relationship of proteasomal impairment and inclusion body formation.

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Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy

Cited by 70 publications

References 23 publications

Primary Progressive Aphasia with Glial Cytoplasmic Inclusions

Primary Progressive Aphasia with Glial Cytoplasmic Inclusions

Axonal Degeneration Induced by Targeted Expression of Mutant Human Tau in Oligodendrocytes of Transgenic Mice That Model Glial Tauopathies

Proteolytic Stress Causes Heat Shock Protein Induction, Tau Ubiquitination, and the Recruitment of Ubiquitin to Tau-Positive Aggregates in Oligodendrocytes in Culture

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