Microglia regulate the number of neural precursor cells in the developing cerebral cortex.
Microglia regulate the number of neural precursor cells in the developing cerebral cortex.
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DOI：
10.1523/jneurosci.3441-12.2013
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发表时间：
2013-03-06
期刊：
影响因子：
--
通讯作者：
Noctor SC
中科院分区：
文献类型：
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作者：
Cunningham CL;Martínez-Cerdeño V;Noctor SC
神经发生必须得到适当的调节，以确保细胞的产生不超过生长的大脑皮层的需要，然而我们对抑制神经元产生的机制的理解仍然不完整。我们研究了小胶质细胞在产前和产后发育的猕猴和大鼠大脑皮层中的功能，发现小胶质细胞通过吞噬神经前体细胞来限制皮层神经元的产生。我们发现，当神经发生接近完成时，小胶质细胞选择性地定植在灵长类动物的SVZ和吞噬神经前体细胞。我们发现，在子宫内用四环素使小胶质细胞失活或用氯钠脂质体消除胎儿大脑皮层的小胶质细胞可显著增加神经前体细胞的数量，而在子宫内通过母体免疫激活小胶质细胞可显著减少神经前体细胞的数量。这些数据表明，小胶质细胞在调节发育中的大脑皮层前体细胞池的大小方面发挥着重要作用，扩大了我们对皮层发育调节机制的理解。此外，我们的数据表明，任何改变子宫内小胶质细胞数量或激活状态的因素都可以深刻地影响神经发育和行为结果。
Neurogenesis must be properly regulated to ensure that cell production does not exceed the requirements of the growing cerebral cortex, yet our understanding of mechanisms that restrain neuron production remains incomplete. We investigated the function of microglial cells in the developing cerebral cortex of prenatal and postnatal macaques and rats and show that microglia limit the production of cortical neurons by phagocytosing neural precursor cells. We show that microglia selectively colonize the primate SVZ and phagocytose neural precursor cells as neurogenesis nears completion. We found that de-activating microglia in utero with tetracyclines or eliminating microglia from the fetal cerebral cortex with liposomal clodronate significantly increased the number of neural precursor cells, while activating microglia in utero through maternal immune activation significantly decreased the number of neural precursor cells. These data demonstrate that microglia play a fundamental role in regulating the size of the precursor cell pool in the developing cerebral cortex, expanding our understanding of the mechanisms that regulate cortical development. Furthermore, our data suggest that any factor that alters the number or activation state of microglia in utero can profoundly affect neural development and affect behavioral outcomes.