Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain.
Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain.
复制标题
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
DOI：
10.1016/j.celrep.2016.12.041
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发表时间：
2017-01-10
期刊：
影响因子：
8.8
通讯作者：
Gomez-Nicola D
中科院分区：
文献类型：
--
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
小胶质细胞在大脑发育、内稳态和功能中起着关键作用，人们普遍认为成年小胶质细胞群寿命较长且通过自我更新来维持。然而，小胶质细胞群确切的时空动态尚不清楚。我们在小鼠和人类中发现，小胶质细胞的更新速度非常快，使得整个细胞群在一生中能够更新数次。从出生后晚期到衰老，小胶质细胞的数量保持稳定，并且如脉冲追踪研究、小胶质细胞的体内慢性成像以及使用细胞凋亡失调的小鼠模型所示，是通过增殖和凋亡的时空耦合来维持的。我们的研究结果表明，小胶质细胞群在不断快速地重塑，这拓展了我们对其在维持大脑内稳态中作用的理解。
小胶质细胞群的形成没有单核细胞在围产期的浸润。
在小鼠或人类的一生中，小胶质细胞密度保持非常稳定。
在小鼠和人类大脑中，小胶质细胞在一生中会更新数次。
小胶质细胞的自我更新是通过增殖和凋亡的耦合来维持的。
小胶质细胞内稳态的潜在机制尚不清楚。阿斯丘等人表明，小胶质细胞的自我更新是通过增殖和凋亡的耦合来维持的，从而导致在小鼠或人类的一生中小胶质细胞数量稳定。
Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis. The microglial population is formed without the perinatal infiltration of monocytes The microglial density remains remarkably stable over a mouse or human lifetime In the mouse and human brain, microglia turn over several times during a lifetime Microglia self-renewal is maintained by coupled proliferation and apoptosis The mechanism or mechanisms underlying microglial homeostasis are unknown. Askew et al. show that microglia self-renewal is maintained by coupled proliferation and apoptosis, resulting in a stable microglia number over a mouse or human lifetime.