Layer V cortical neurons require microglial support for survival during postnatal development
Layer V cortical neurons require microglial support for survival during postnatal development
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DOI：
10.1038/nn.3358
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发表时间：
2013-05-01
影响因子：
25
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
--
作者：
Ueno, Masaki;Fujita, Yuki;Yamashita, Toshihide
神经元在神经回路形成过程中需要营养支持；然而，细胞环境如何对神经元存活做出贡献仍不清楚。我们发现，在出生后发育过程中，V层皮质神经元需要小胶质细胞的支持才能存活。具体地说，我们发现小胶质细胞在出生后大脑中靠近大脑下投射轴突和穹隆投射轴突的地方聚集。在CD11b-DTR转基因小鼠中，用二甲胺四环素灭活小胶质细胞或一过性切除小胶质细胞会导致细胞凋亡增加，尤其是在V层脑下投射神经元和膝状体投射神经元。小胶质细胞中的CX3CR1是V层神经元存活所必需的。小胶质细胞持续促进体外培养的皮质神经元存活。此外，我们还发现小胶质细胞来源的IGF1是维持神经元存活的营养因子。我们的结果突出了神经元-神经胶质细胞的相互作用，这对于大脑发育中的特定时期的网络形成是不可或缺的。
Neurons require trophic support during neural circuit formation; however, how the cellular milieu contributes to neuronal survival remains unclear. We found that layer V cortical neurons require support from microglia for survival during postnatal development. Specifically, we found that microglia accumulated close to the subcerebral and callosal projection axons in the postnatal brain. Inactivation of microglia by minocycline treatment or transient ablation of microglia in CD11b-DTR transgenic mice led to increased apoptosis, specifically in layer V subcerebral and callosal projection neurons. CX3CR1 in microglia was required for the survival of layer V neurons. Microglia consistently promoted the survival of cortical neurons in vitro. In addition, we identified microglia-derived IGF1 as a trophic factor that maintained neuronal survival. Our results highlight a neuron-glia interaction that is indispensable for network formation during a specific period in the developing brain.