1. SRC-1 Deficiency Increases Susceptibility of Mice to Depressive-Like Behavior After Exposure to CUMS
- Author
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Jin-Yi Yang, Xue-Fei Wu, Shao Li, Xuan Zhang, Bin Wang, Qiong Wu, Michael Ntim, Xue-Yan Na, and Yu-Hui Yuan
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Hippocampus ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Nuclear Receptor Coactivator 1 ,0302 clinical medicine ,Glucocorticoid receptor ,Pregnancy ,Internal medicine ,Animals ,Medicine ,Cells, Cultured ,Neuroinflammation ,Mice, Knockout ,Depression ,business.industry ,General Medicine ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Hindlimb Suspension ,Nuclear receptor ,Hypothalamus ,Knockout mouse ,Female ,Microglia ,business ,Stress, Psychological ,030217 neurology & neurosurgery ,Glucocorticoid ,Hormone ,medicine.drug - 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.
- Published
- 2021
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