A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions in the pontine and inferior olivary nuclei in multiple system atrophy
Abstract
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by the presence of neuronal and oligodendroglial α‐synuclein aggregates. To investigate the relationship between the occurrence of neuronal cytoplasmic and intranuclear inclusions (NCIs and NNIs, respectively) and the progression of neuronal degeneration, we performed a quantitative analysis of the pontine and inferior olivary nuclei based on 14 cases of MSA. α‐Synuclein immunohistochemistry revealed that NCIs and NNIs were present in both brain nuclei in all the cases. The average incidence of NCIs in the pontine and inferior olivary nuclei was 9.1% and 25.8%, respectively, and that of NNIs was 9.2% and 9.0%, respectively. The number of NNIs was strongly correlated with that of neurones in the pontine and inferior olivary nuclei. Although the number of NCIs was not correlated with the neuronal population in both nuclei, the NCI count in patients with moderate MSA was higher than in patients with mild MSA. The NNI count was much higher than the NCI count in the pontine nucleus in four patients, and was the same in the olivary nucleus in three of the four patients. Moreover, the neuronal population in the NNI‐predominant cases was significantly higher than in the NCI‐predominant cases. These findings suggest that NCI formation is accelerated by the progression of the disease process, and that in MSA, NNI formation is an earlier phenomenon than NCI formation.
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The pathological hallmark of MSA is abnormal accumulation of α-syn in the cytoplasm of oligodendrocytes, named glial cytoplasmic inclusions (GCIs).
“The pathological hallmark of MSA is the abnormal accumulation of α-syn in the cytoplasm of oligodendrocytes, named glial cytoplasmic inclusions (GCIs).271–275”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [274]
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- Authors
- Nishie, M., Mori, F., Yoshimoto, M., Takahashi, H., & Wakabayashi, K.
- Affiliations
- Hirosaki University (JP)
- Taisho Pharmaceutical (Japan) (JP)
- Brain Research Institute, Niigata University (JP)
- Corresponding author
- Nishie, M.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2004-05-04
- Volume
- 30
- Issue
- 5
- Pages
- 546-554
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2042448415
- Cited by
- 123
- References
- 47
- Citations by year
- 2025: 6 · 2024: 10 · 2023: 5 · 2022: 14 · 2021: 11 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 7
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Naito Foundation
- Uehara Memorial Foundation
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- multiple system atrophy, alpha-synuclein, neuronal cytoplasmic inclusions, intranuclear inclusions, pontine nuclei, inferior olive, neurodegeneration, disease progression, oligodendroglial inclusions, synucleinopathies
- MeSH terms
- Aged, Aged, 80 and over, Inclusion Bodies, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Tissue Proteins, Neurons, Olivary Nucleus, Pons, Microscopy, Immunoelectron, Multiple System Atrophy, Intranuclear Inclusion Bodies, Synucleins, alpha-Synuclein
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