Microglial Activation Parallels System Degeneration in Multiple System Atrophy
Abstract
Multiple system atrophy (MSA) is a neurodegenerative disorder that predominantly affects motor-related neuroanatomic structures. The role of microglia in MSA is unknown. To address this issue, we conducted quantitative image studies on the brains from 13 cases of MSA, comprising 8 cerebellar and 5 parkinsonian variants. Microglial and glial cytoplasmic inclusion (GCI) burdens were determined with image analysis on brain sections immunostained with antibodies to HLA-DR and alpha-synuclein. Many activated microglia, as well as GCIs, were noted in motor-related structures, including the cerebellar input, extrapyramidal motor, and pyramidal motor structures, but not in the cerebellar output structures. This result indicates that microglial activation, as well as the distribution of GCIs, is system-specific in MSA. The correlation analysis between the microglial and GCI burdens yielded variable yet significant correlations in the cerebellar input, extrapyramidal motor, and pyramidal motor systems, but not in the cerebellar output system. This result suggests that microglial activation is at least partly determined by GCIs or oligodendroglial alpha-synuclein in specific neuroanatomic systems affected in MSA. Taken together, considering the known toxic effects of microglia in neurodegenerative diseases, microglia may play a part in the development of system-specific tissue injuries, contributing to the system-bound clinical and pathological phenotypes.
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Activated microglia are found within white matter tracts and areas of neurodegeneration in patients with MSA, and are believed to release proinflammatory cytokines and possibly play a role in neurodegeneration.
“It has been reported that activated microglia are found within white matter tracts and areas of neurodegeneration in patients with MSA, and are believed to release proinflammatory cytokines and possibly play a role in neurodegeneration [26, 53].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [26]
Histopathologically, microglial activation is prominent in regions of motor-related structures, including cerebellar input, extrapyramidal and pyramidal motor structures, in MSA.
“Histopathologically, microglial activation was found to be prominent in regions of motor-related structures, including cerebellar input, extrapyramidal and pyramidal motor structures”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [283]
Microglial activation likely promotes neurodegeneration in MSA.
“which suggests that microglial activation likely promotes neurodegeneration in MSA.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [283]
According to pathological studies and PET imaging of MSA brains, microglial activation and neuroinflammation constitute important features of MSA.
“But according to pathological studies and PET imaging of MSA brains, microglial activation and neuroinflammation constitute important features of MSA.283–287”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [283]
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- Authors
- Ishizawa, K., Komori, T., Sasaki, S., Arai, N., Mizutani, T., & Hirose, T.
- Affiliations
- Saitama Medical University (JP)
- Tokyo Women's Medical University (JP)
- Tokyo Metropolitan Neurological Hospital (JP)
- Corresponding author
- Ishizawa, Keisuke
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01
- Volume
- 63
- Issue
- 1
- Pages
- 43-52
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2307330333
- Cited by
- 172
- References
- 45
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 9 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 14 · 2019: 9 · 2018: 13 · 2017: 10 · 2016: 8 · 2015: 12 · 2014: 10 · 2013: 11 · 2012: 8
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (11670201)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- multiple system atrophy, microglial activation, glial cytoplasmic inclusions, alpha-synuclein, HLA-DR, extrapyramidal system, cerebellar output, neurodegeneration
- MeSH terms
- Aged, Brain, Inclusion Bodies, Female, HLA-DR Antigens, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Male, Middle Aged, Nerve Tissue Proteins, Microglia, Multiple System Atrophy, Synucleins, alpha-Synuclein
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