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SRC-1 Deficiency Increases Susceptibility of Mice to Depressive-Like Behavior After Exposure to CUMS

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Abstract

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.

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Acknowledgements

This work was supported by grants from Liaoning Provincial Key R&D Program (2019020048-JH2/103); Liaoning Revitalization Talents Program (XLYC1902044, XLYC1808031); The State Key Program of National Natural Science Foundation of China (U1908208); The National Natural Science Foundation of China (30973519); Liaoning Provincial Doctoral Research Fund (2019-BS-064) and Natural Science Foundation of Liaoning province of China (2015020672, 201602218).

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  1. Qiong Wu, Bin Wang and Michael Ntim contributed equally to this work.

Authors and Affiliations

  1. Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China

    Qiong Wu, Bin Wang, Michael Ntim, Xue-Yan Na, Xue-Fei Wu & Shao Li

  2. National-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China

    Xuan Zhang

  3. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China

    Yu-Hui Yuan

  4. Department of Urology, Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, China

    Jin-Yi Yang

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  1. Qiong Wu
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Wu, Q., Wang, B., Ntim, M. et al. SRC-1 Deficiency Increases Susceptibility of Mice to Depressive-Like Behavior After Exposure to CUMS. Neurochem Res 46, 1830–1843 (2021). https://doi.org/10.1007/s11064-021-03316-y

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