Microglia Engulf Viable Newborn Cells in the Epileptic Dentate Gyrus
Microglia Engulf Viable Newborn Cells in the Epileptic Dentate Gyrus
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DOI：
10.1002/glia.23018
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发表时间：
2016-09-01
期刊：
影响因子：
6.2
通讯作者：
Ikegaya, Yuji
中科院分区：
文献类型：
--
作者：
Luo, Cong;Koyama, Ryuta;Ikegaya, Yuji
小胶质细胞是大脑的常驻免疫细胞，在成体神经发生过程中吞噬齿状回 (DG) 颗粒下区 (SGZ) 中死亡的神经祖细胞。癫痫持续状态（SE）后SGZ中的新生细胞数量显着增加，但SE后小胶质细胞是否以及如何调节新生细胞数量仍不清楚。在这里，我们发现小胶质细胞在 SE 后通过初级吞噬作用快速消除新生细胞，这是一个活细胞被吞噬的过程，从而调节纳入 DG 的新生细胞的数量。 SE后5天，成年小鼠大脑中DG中的新生细胞数量有所增加，但在一周内迅速下降至对照水平。在此期间，DG中的小胶质细胞高度活跃并吞噬新生细胞。我们发现大多数被吞噬的新生细胞是半胱天冬酶阴性的活细胞。最后，用米诺环素灭活小胶质细胞可以维持 SE 后新生细胞数量的增加。此外，SE 后米诺环素治疗诱导肺门异位颗粒细胞的出现。因此，我们的研究结果表明，小胶质细胞可能通过初级吞噬作用消除 SE 后多余的新生细胞，从而有助于齿状神经源性生态位的稳态。
Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase-negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis.