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J Neuropathol Exp Neurol. 2004 Jan;63(1):43-52.

Microglial activation parallels system degeneration in multiple system atrophy.

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  • 1Department of Pathology, Saitama Medical School, Saitama, Japan.


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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