CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.

Autor: Chen X; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Cui QQ; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Hu XH; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Ye J; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Liu ZC; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Mei YX; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Wang F; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.; The Research Center for Depression, Tongji Medical College, Huazhong University of Science, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China., Hu ZL; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. zlhu916@hust.edu.cn.; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China. zlhu916@hust.edu.cn.; The Research Center for Depression, Tongji Medical College, Huazhong University of Science, Wuhan, 430030, China. zlhu916@hust.edu.cn.; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China. zlhu916@hust.edu.cn., Chen JG; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. chenj@mails.tjmu.edu.cn.; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China. chenj@mails.tjmu.edu.cn.; The Research Center for Depression, Tongji Medical College, Huazhong University of Science, Wuhan, 430030, China. chenj@mails.tjmu.edu.cn.; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, China. chenj@mails.tjmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2023 Jun 30; Vol. 20 (1), pp. 157. Date of Electronic Publication: 2023 Jun 30.
DOI: 10.1186/s12974-023-02836-4
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusions: Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.
(© 2023. The Author(s).)
Databáze: MEDLINE
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