Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis.

Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis.
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DOI:
10.1016/j.stem.2010.08.014
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发表时间:
2010-10-08
期刊:
影响因子:
23.9
通讯作者:
Maletic-Savatic, Mirjana
Maletic-Savatic, Mirjana
中科院分区:
医学1区
文献类型:
--
作者:
Sierra, Amanda;Encinas, Juan M.;Deudero, Juan J. P.;Chancey, Jessica H.;Enikolopov, Grigori;Overstreet-Wadiche, Linda S.;Tsirka, Stella E.;Maletic-Savatic, Mirjana

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在成年海马中,齿状回亚颗粒区(SGZ)的神经祖细胞产生新生的神经母细胞。然而,这些细胞中只有一小部分在四周后整合到海马体回路中成为成熟的神经元。在这里,我们发现大多数新生细胞在其生命的最初一到四天内,在从扩增神经祖细胞向神经母细胞过渡的过程中,通过凋亡死亡。这些凋亡的新生细胞通过吞噬作用被存在于成人SGZ生态位的未受挑战的小胶质细胞迅速清除。小胶质细胞的吞噬作用是有效的,不受年龄增长或炎症挑战的影响。我们的研究结果表明,新生细胞存活的主要关键时期发生在出生后的几天内,并揭示了小胶质细胞在维持基线神经源级联稳态中的新作用。
In the adult hippocampus, neuroprogenitor cells in the subgranular zone (SGZ) of the dentate gyrus give rise to newborn neuroblasts. However, only a small subset of these cells integrates into the hippocampal circuitry as mature neurons at the end of a four-week period. Here, we show that the majority of the newborn cells undergo death by apoptosis in the first one to four days of their life, during the transition from amplifying neuroprogenitors to neuroblasts. These apoptotic newborn cells are rapidly cleared out through phagocytosis by unchallenged microglia present in the adult SGZ niche. Phagocytosis by the microglia is efficient and undeterred by increased age or inflammatory challenge. Our results suggest that the main critical period of newborn cell survival occurs within a few days of birth and reveal a new role for microglia in maintaining the homeostasis of the baseline neurogenic cascade.
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