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Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat Stress Induced Depression Mouse

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Abstract

Inflammation recently has been considered to be participated in the pathogenesis of major depressive disorder (MDD). However, the detailed mechanism of inflammation in depression has not been completely understood yet. In the present study, depression mice model was established by chronic social defeat stress (CSDS) method and confirmed by behavior examinations including forced swimming test and sucrose preference test. The decrease of spine density and postsynaptic density protein 95 (PSD95) in hippocampus further verified the depression model. Then, the microglia polarization state and endoplasmic reticulum (ER) stress were investigated. At transcriptional level, M1 marker (inducible nitric oxide synthase (iNOS), CD16, CD86, CXCL10) in CSDS mice was higher than that in control group while there was no difference in M2 marker (Arginase and CD206) between two groups. And it was observed in the hippocampus of CSDS induced depression mice that increased activated microglia was merged with iNOS instead of arginase by immunofluorescence staining. Furthermore, the M1 marker Interleukin (IL)-1β and tumor necrosis factor (TNF)-α were increased in depression mice while the M1 marker IL-6 and M2 marker IL-10 remained unchanged. The expression of ER stress signaling factors, including protein kinase RNA-like ER kinase (PERK), Phosphorylated α-subunit of eukaryotic translation initiation factor 2(p-eIF2α), C/EBP homologous protein (CHOP), and X-box binding protein 1(XBP1) were significantly higher in CSDS-induced depression mice than in control mice. In all, our results suggest that M1 polarization and ER stress play a vital role in MDD pathogenesis.

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Acknowledgements

This study was supported by Grants from the National Natural Science Foundation of China (No. 81671151; No. 81371414).

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  1. Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Zhong Road, Shanghai, 200040, China

    Jie Tang, Wenbo Yu, Sheng Chen, Zidan Gao & Baoguo Xiao

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Correspondence to Baoguo Xiao.

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Tang, J., Yu, W., Chen, S. et al. Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat Stress Induced Depression Mouse. Neurochem Res 43, 985–994 (2018). https://doi.org/10.1007/s11064-018-2504-0

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