Synaptic elimination by microglia and disturbed higher brain functions
Synaptic elimination by microglia and disturbed higher brain functions
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DOI：
10.1016/j.neuint.2020.104901
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发表时间：
2021-01-01
影响因子：
4.2
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
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作者：
Miyanishi, Kazuya;Sato, Arisa;Tanaka, Junya
长期以来，人们一直认为正常成熟大脑中的小胶质细胞是处于休眠状态的细胞，直到病理事件发生，激活小胶质细胞。然而，目前已知的是，正常成熟大脑中具有静息分支形态的小胶质细胞在脑实质和吞噬突触中活跃活动，从而形成和维持神经回路。本文综述了近年来关于小胶质细胞在成熟大脑中的作用的研究成果，特别提到了突触吞噬和高级脑功能。小胶质细胞吞噬消除突触可能影响兴奋性和抑制性突触传递之间的平衡，称为E/I平衡。当小胶质细胞突触消除受损导致E/I平衡紊乱时，大脑功能可能出现各种问题：记忆和认知功能、睡眠、运动、社会行为和思维。除了小胶质细胞在正常发育和成熟大脑中的作用外，小胶质细胞吞噬功能受损还与神经、精神和发育障碍引起的这些高级脑功能紊乱有关；帕金森氏症和阿尔茨海默氏症、自闭症谱系障碍、注意力缺陷/多动障碍和精神分裂症。
Microglial cells in normal mature brains have long been considered to be cells that are resting until pathological events take place, activating the microglial cells. However, it is currently well known that the microglia that have resting ramified morphology in normal mature brains move actively in the brain parenchyma and phagocytose synapses, thus forming and maintaining neural circuits. This review summarizes recent findings on the roles of microglia in mature brains, with special reference to phagocytosis of synapses and higher brain functions. Phagocytic elimination of synapses by microglia may affect the balance between excitatory and inhibitory synaptic transmission, termed the E/I balance. When impaired synaptic elimination by microglia leads to disturbed E/I balance, various problems may follow in brain functions: in memory and cognitive functions, sleep, movement, social behaviors, and thinking. In addition to the roles of microglia in normal developing and mature brains, impaired microglial phagocytosis functions also correlate with disturbances to these higher brain functions that are caused by neurological, mental, and developmental disorders; Parkinson's and Alzheimer's diseases, autism spectrum disorder, attention deficit/hyperactivity disorder, and schizophrenia.