Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
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DOI：
10.1126/sciadv.aba3239
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发表时间：
2020-06-01
期刊：
影响因子：
13.6
通讯作者：
Grutzendler, Jaime
中科院分区：
文献类型：
--
作者：
Damisah, Eyiyemisi C.;Hill, Robert A.;Grutzendler, Jaime
细胞死亡在整个生命中都很普遍，然而，吞噬细胞在活体大脑中清除身体过程中的协调相互作用和作用却知之甚少。我们开发了光化学和病毒方法来诱导单细胞死亡，并将其与活体光学成像相结合。这种方法使我们能够以精确的时空分辨率跟踪多细胞吞噬细胞的相互作用。星形胶质细胞和小胶质细胞以一种协调和同步的方式与死亡的神经元接触。每个胶质细胞都扮演着特殊的角色：星形胶质细胞突起迅速极化并吞噬大量树突状的小凋亡小体，而小胶质细胞迁移并吞噬胞体和顶端树突。每个神经胶质细胞的相对参与和吞噬特化是可塑性的，并受受体酪氨酸激酶MerTK控制。在衰老过程中，凋亡细胞的清除有明显的延迟。因此，在身体搬运过程中，精确协调的反应和神经胶质细胞之间的串扰可能是维持大脑内环境稳定的关键。
Cell death is prevalent throughout life; however, the coordinated interactions and roles of phagocytes during corpse removal in the live brain are poorly understood. We developed photochemical and viral methodologies to induce death in single cells and combined this with intravital optical imaging. This approach allowed us to track multicellular phagocytic interactions with precise spatiotemporal resolution. Astrocytes and microglia engaged with dying neurons in an orchestrated and synchronized fashion. Each glial cell played specialized roles: Astrocyte processes rapidly polarized and engulfed numerous small dendritic apoptotic bodies, while microglia migrated and engulfed the soma and apical dendrites. The relative involvement and phagocytic specialization of each glial cell was plastic and controlled by the receptor tyrosine kinase Mertk. In aging, there was a marked delay in apoptotic cell removal. Thus, a precisely orchestrated response and cross-talk between glial cells during corpse removal may be critical for maintaining brain homeostasis.