Pan Kuang, Garaschuk Olga
Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany.
J Physiol. 2023 Oct;601(19):4203-4215. doi: 10.1113/JP279521. Epub 2022 Apr 6.
Under physiological conditions microglia, the immune sentinels of the brain, constantly monitor their microenvironment. In the case of danger, damage or cell/tissue dyshomeostasis, they react with changes in process motility, polarization, directed process movement, morphology and gene expression profile; release pro- and anti-inflammatory mediators; proliferate; and clean brain parenchyma by means of phagocytosis. Based on recent transcriptomic and in vivo Ca imaging data, we argue that the local cell/tissue dyshomeostasis is sensed by microglia via intracellular Ca signals, many of which are mediated by Ca release from the intracellular Ca stores. These signals encode the strength, duration and spatiotemporal pattern of the stimulus and, at the same time, relay this information further to trigger the respective Ca -dependent effector pathways. We also point to the fact that microglial Ca signalling is sexually dimorphic and undergoes profound changes across the organism's lifespan. Interestingly, the first changes in microglial Ca signalling are visible already in 9- to 11-month-old mice, roughly corresponding to 40-year-old humans.
在生理条件下，小胶质细胞作为大脑的免疫哨兵，不断监测其微环境。在面临危险、损伤或细胞/组织内环境失衡时，它们会通过突起运动性、极化、定向突起运动、形态和基因表达谱的变化做出反应；释放促炎和抗炎介质；增殖；并通过吞噬作用清理脑实质。基于最近的转录组学和体内钙成像数据，我们认为小胶质细胞通过细胞内钙信号感知局部细胞/组织内环境失衡，其中许多信号是由细胞内钙库释放钙介导的。这些信号编码刺激的强度、持续时间和时空模式，同时将此信息进一步传递以触发各自的钙依赖效应途径。我们还指出，小胶质细胞钙信号存在性别差异，并且在生物体的整个生命周期中会发生深刻变化。有趣的是，小胶质细胞钙信号的最初变化在9至11个月大的小鼠中就已可见，大致相当于40岁的人类。
