小胶质细胞
树突棘
炎症
CX3CR1型
谷氨酸的
脂多糖
扣带皮质
扣带回前部
神经科学
受体
生物
心理学
谷氨酸受体
医学
免疫学
内科学
趋化因子
海马结构
中枢神经系统
趋化因子受体
认知
作者
Peng Cao,Changmao Chen,An Liu,Qing-Hong Shan,Xia Zhu,Chun-Hui Jia,Xiaoqi Peng,Mingjun Zhang,Zahra Farzinpour,Wenjie Zhou,Haitao Wang,Jiang‐Ning Zhou,Xiaoyuan Song,Liecheng Wang,Wenjuan Tao,Chao Zheng,Yan Zhang,Yu‐Qiang Ding,Yan Jin,Lin Xu,Zhi Zhang
出处
期刊:Neuron
[Elsevier]
日期:2021-08-01
卷期号:109 (16): 2573-2589.e9
被引量:153
标识
DOI:10.1016/j.neuron.2021.06.012
摘要
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.
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