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

• Published in: Neurochemical research 2021-07, Vol.46 (7), p.1830-1843
• Main Authors: Wu, Qiong, Wang, Bin, Ntim, Michael, Zhang, Xuan, Na, Xue-Yan, Yuan, Yu-Hui, Wu, Xue-Fei, Yang, Jin-Yi, Li, Shao
• Format: Article
• Language: English
• Subjects: Adrenal glands; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Cells, Cultured; Depression - etiology; Depression - metabolism; Female; Glucocorticoids; Hindlimb Suspension; Hippocampus - metabolism; Hormones; Hypothalamus; Inflammation; Lipopolysaccharides; Male; Mental depression; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Microglia - metabolism; Neurochemistry; Neurology; Neurosciences; Nuclear Receptor Coactivator 1 - deficiency; Nuclear Receptor Coactivator 1 - metabolism; Nuclear receptors; Original Paper; Pituitary; Pregnancy; Receptors; Risk analysis; Risk factors; Steroid hormones; Steroid receptor coactivator 1; Steroids; Stress; Stress, Psychological - complications; Stress, Psychological - metabolism
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-021-03316-y

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.