PMID- 33881662 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20240226 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 46 IP - 7 DP - 2021 Jul TI - SRC-1 Deficiency Increases Susceptibility of Mice to Depressive-Like Behavior After Exposure to CUMS. PG - 1830-1843 LID - 10.1007/s11064-021-03316-y [doi] AB - Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear receptors (NRs) when NRs are activated by steroid hormones, such as glucocorticoid. SRC-1 is abundant in hippocampus and hypothalamus and is also related to some major risk factors for depression, implicated by its reduced expression after stress and its effect on hypothalamus-pituitary-adrenal gland axis function. However, whether SRC-1 is involved in the formation of depression remains unclear. In this study, we firstly established chronic unpredictable stress (CUS) to induce depressive-like behaviors in mice and found that SRC-1 expression was reduced by CUS. A large number of studies have shown that neuroinflammation is associated with stress-induced depression and lipopolysaccharide (LPS) injection can lead to neuroinflammation and depressive-like behaviors in mice. Our result indicated that LPS treatment also decreased SRC-1 expression in mouse brain, implying the involvement of SRC-1 in the process of inflammation and depression. Next, we showed that the chronic unpredictable mild stress (CUMS) failed to elicit the depressive-like behaviors and dramatically promoted the expression of SRC-1 in brain of wild type mice. What's more, the SRC-1 knockout mice were more susceptible to CUMS to develop depressive-like behaviors and presented the changed expression of glucocorticoid receptor. However, SRC-1 deficiency did not affect the microglia activation induced by CUMS. Altogether, these results indicate a correlation between SRC-1 level and depressive-like behaviors, suggesting that SRC-1 might be involved in the development of depression induced by stress. FAU - Wu, Qiong AU - Wu Q AD - Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China. FAU - Wang, Bin AU - Wang B AD - Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China. FAU - Ntim, Michael AU - Ntim M AD - Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China. FAU - Zhang, Xuan AU - Zhang X AD - National-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China. FAU - Na, Xue-Yan AU - Na XY AD - Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China. FAU - Yuan, Yu-Hui AU - Yuan YH AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Wu, Xue-Fei AU - Wu XF AD - Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China. wuxuefei1973@126.com. FAU - Yang, Jin-Yi AU - Yang JY AD - Department of Urology, Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, China. yangjinyi90@hotmail.com. FAU - Li, Shao AU - Li S AD - Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China. lishao89@dmu.edu.cn. LA - eng GR - 2019020048-JH2/103/Liaoning Provincial Key R&D Program/ GR - XLYC1902044/Liaoning Revitalization Talents Program/ GR - XLYC1808031/Liaoning Revitalization Talents Program/ GR - U1908208/The State Key Program of National Natural Science Foundation of China/ GR - 2019-BS-064/Liaoning Provincial Doctoral Research Fund/ GR - 2015020672/Natural Science Foundation of Liaoning province of China/ GR - 201602218/Natural Science Foundation of Liaoning province of China/ PT - Journal Article DEP - 20210421 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - EC 2.3.1.48 (Ncoa1 protein, mouse) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM MH - Animals MH - Cells, Cultured MH - Depression/etiology/*metabolism MH - Female MH - Hindlimb Suspension MH - Hippocampus/metabolism MH - Male MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microglia/metabolism MH - Nuclear Receptor Coactivator 1/*deficiency/metabolism MH - Pregnancy MH - Stress, Psychological/complications/*metabolism MH - Mice OTO - NOTNLM OT - Depressive-like behavior OT - Glucocorticoid receptor OT - Microglia activation OT - Steroid receptor coactivator-1 OT - Stress EDAT- 2021/04/22 06:00 MHDA- 2021/10/21 06:00 CRDT- 2021/04/21 12:22 PHST- 2020/03/04 00:00 [received] PHST- 2021/03/29 00:00 [accepted] PHST- 2021/03/24 00:00 [revised] PHST- 2021/04/22 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/04/21 12:22 [entrez] AID - 10.1007/s11064-021-03316-y [pii] AID - 10.1007/s11064-021-03316-y [doi] PST - ppublish SO - Neurochem Res. 2021 Jul;46(7):1830-1843. doi: 10.1007/s11064-021-03316-y. Epub 2021 Apr 21.