齿状回
神经发生
海马结构
神经科学
神经干细胞
细胞生物学
基因敲除
血小板源性生长因子受体
生长因子
海马体
生物
受体
干细胞
生物化学
细胞培养
遗传学
作者
Hou-Hong Li,Yang Liu,Hongsheng Chen,Wang Ji,Yu-Ke Li,Yang Zhao,Rui Sun,Jin‐Gang He,Fang Wang,Jian-Guo Chen
标识
DOI:10.1002/advs.202301110
摘要
Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive-like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)-dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)-induced depression-like behavior. Further analysis exhibits that inhibition of gamma-aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+ -DG) increases the expression of platelet-derived growth factor-BB (PDGF-BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant-like effects. Overexpression of the PDGF-BB or exogenous administration of PDGF-BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult-born hippocampal neurons, as well as on depressive-like behaviors. Conversely, knockdown of PDGF-BB facilitates CSDS-induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet-derived growth factor receptor beta (PDGFRβ) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF-BB. These results delineate a previously unidentified PDGF-BB/PDGFRβ signaling in regulating depressive-like behaviors and identify a novel mechanism by which the MSGABA+ -DG pathway regulates the expression of PDGF-BB in SOM-positive interneurons.
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