Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation
Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation
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DOI：
10.1016/j.celrep.2019.05.015
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发表时间：
2019-06-04
期刊：
影响因子：
8.8
通讯作者：
Koyama, Ryuta
中科院分区：
文献类型：
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作者：
Andoh, Megumi;Shibata, Kazuki;Koyama, Ryuta
通常认为患有神经发育障碍的个体的异常行为是不可逆转的。在这里，我们表明，自愿跑轮可以改善在母体免疫激活（MIA）引起的神经发育障碍小鼠模型中观察到的社交性、重复性和焦虑异常。运动会激活部分齿状颗粒细胞，使海马 CA3 突触密度正常化，而在受 MIA 影响的后代中，海马 CA3 突触密度过高。 MIA 后代的突触过剩是由小胶质细胞突触吞噬的缺陷引起的，而小胶质细胞激活可以通过锻炼使突触正常化。最后，化学遗传学诱导的颗粒细胞激活促进 CA3 突触的吞噬。因此，我们的研究提出了自愿运动在调节神经发育障碍的行为和突触异常中的作用。
Abnormal behaviors in individuals with neurodevelopmental disorders are generally believed to be irreversible. Here, we show that voluntary wheel running ameliorates the abnormalities in sociability, repetitiveness, and anxiety observed in a mouse model of a neurodevelopmental disorder induced by maternal immune activation (MIA). Exercise activates a portion of dentate granule cells, normalizing the density of hippocampal CA3 synapses, which is excessive in the MIA-affected offspring. The synaptic surplus in the MIA offspring is induced by deficits in synapse engulfment by microglia, which is normalized by exercise through microglial activation. Finally, chemogenetically induced activation of granule cells promotes the engulfment of CA3 synapses. Thus, our study proposes a role of voluntary exercise in the modulation of behavioral and synaptic abnormalities in neurodevelopmental disorders.