Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines
作者：Peng Cao, Changmao Chen, An Liu, Qinghong Shan, Xia Zhu, Chunhui Jia, Xiaoqi Peng, Mingjun Zhang, Zahra Farzinpour, Wenjie Zhou, Haitao Wang, Jiang-Ning Zhou, Xiaoyuan Song, Liecheng Wang, Wenjuan Tao, Changjian Zheng, Yan Zhang, Yu-Qiang Ding, Zhi Zhang
期刊：Neuron
發(fā)表時間：2021/07/06
Early-life inflammation increases the risk for depression in later life. Here, we demonstrate how early-life inflammation causes adolescent depressive-like symptoms: by altering the long-term neuronal spine engulfment capacity of microglia. For mice exposed to lipopolysaccharide (LPS)-induced inflammation via the Toll-like receptor 4/NF-κB signaling pathway at postnatal day (P) 14, ongoing longitudinal imaging of the living brain revealed that later stress (delivered during adolescence on P45) increases the extent of microglial engulfment around anterior cingulate cortex (ACC) glutamatergic neuronal (ACCGlu) spines. When the ACC microglia of LPS-treated mice were deleted or chemically inhibited, the mice did not exhibit depressive-like behaviors during adolescence. Moreover, we show that the fractalkine receptor CX3CR1 mediates stress-induced engulfment of ACCGlu neuronal spines. Together, our findings establish that early-life inflammation causes dysregulation of microglial engulfment capacity, which encodes long-lasting maladaptation of ACCGlu neurons to stress, thus promoting development of depression-like symptoms during adolescence.
