CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.
CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.
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齿状回中的CD200通过减轻小胶质细胞的过度激活而促进海马神经发生，从而改善小鼠的抑郁样行为。
DOI：
10.1186/s12974-023-02836-4
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发表时间：
2023-06-30
影响因子：
9.3
通讯作者：
Chen, Jian-Guo
中科院分区：
文献类型：
--
作者：
Chen, Xi;Cui, Qian-Qian;Hu, Xiao-Hai;Ye, Jian;Liu, Zi-Cun;Mei, Yuan-Xi;Wang, Fang;Hu, Zhuang-Li;Chen, Jian-Guo
神经炎症和小胶质细胞在抑郁症的发展中起着关键作用。分化簇200（CD 200）是一种主要在神经元中表达的抗炎糖蛋白，其受体CD 200 R1主要在小胶质细胞中表达。虽然CD 200-CD 200 R1通路是小胶质细胞活化所必需的，但其在抑郁症的病理生理学中的作用仍然未知。采用慢性社会失败应激（CSDS）结合行为学测试，探讨CD 200对抑郁样行为的影响。使用病毒载体来过表达或敲低CD 200。采用分子生物学技术检测CD 200和炎性细胞因子水平。免疫荧光法检测小胶质细胞状态、BDNF表达及神经发生情况。我们发现，经历CSDS的小鼠齿状回（DG）区域CD 200的表达减少。过度表达CD 200可减轻应激小鼠的抑郁样行为，抑制CD 200可增加应激易感性。当小胶质细胞上的CD 200 R1受体被敲低时，CD 200就无法发挥其缓解抑郁样行为的作用。DG脑区的小胶质细胞在暴露于CSDS后形态学上被激活。与此相反，外源性给予CD 200抑制小胶质细胞过度活化，减轻海马神经炎症反应，并增加BDNF的表达，这反过来又改善了成年海马神经发生障碍的DG由CSDS诱导。总之，这些结果表明，CD 200介导的小胶质细胞过度活化的缓解有助于小鼠齿状回神经发生的抗抑郁作用。在线版本包含补充材料，可通过10.1186/s12974-023-02836-4获得。
Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200–CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice. The online version contains supplementary material available at 10.1186/s12974-023-02836-4.
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影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
影响因子：
9.3
作者：
通讯作者：
--
DOI：
10.1097/nen.0b013e3181964113
发表时间：
2009-02-01
影响因子：
3.2
作者：
Koning, Nathalie;Swaab, Dick F.;Huitinga, Inge
通讯作者：
Huitinga, Inge
影响因子：
5.9
作者：
Benameur T;Soleti R;Porro C
通讯作者：
Porro C
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影响因子：
7.7
作者：
Cui, Qian-Qian;Hu, Zhuang-Li;Wang, Fang
通讯作者：
Wang, Fang