Microglial activation parallels system degeneration in multiple system atrophy
Microglial activation parallels system degeneration in multiple system atrophy
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DOI：
10.1093/jnen/63.1.43
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发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Hirose, T
中科院分区：
文献类型：
--
作者：
Ishizawa, K;Komori, T;Hirose, T
多系统萎缩（MSA）是一种神经退行性疾病，主要影响运动相关的神经解剖结构。小胶质细胞在MSA中的作用尚不清楚。为了解决这个问题，我们对13例MSA的大脑进行了定量图像研究，其中包括8例小脑和5例帕金森变异。小胶质细胞和胶质细胞胞质内含物（GCI）的负担，确定与HLA-DR和α-突触核蛋白的抗体免疫染色的脑切片的图像分析。许多激活的小胶质细胞，以及GCI，注意到在运动相关的结构，包括小脑输入，锥体外运动，锥体运动结构，但不是在小脑输出结构。这一结果表明，小胶质细胞活化，以及GCI的分布，是系统特异性的MSA。小胶质细胞和GCI负担之间的相关性分析产生了变量，但在小脑输入，锥体外系运动，锥体运动系统，但不是在小脑输出系统的显着相关性。这一结果表明，小胶质细胞活化至少部分地由GCI或少突胶质细胞α-突触核蛋白在特定的神经解剖系统中受影响的MSA。加在一起。考虑到小胶质细胞在神经变性疾病中的已知毒性作用，小胶质细胞可能在系统特异性组织损伤的发展中起作用，促成系统结合的临床和病理表型。
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.