Oleanolic acid decreases SGK1 in the hippocampus in corticosterone-induced mice

Our previous study has demonstrated that oleanolic acid produced an antidepressant-like effect in mice exposed to chronic stress. Considering that serine/threonine-protein kinase 1 (SGK1) is involved in stress response, the present study aimed to evaluate the involvement of SGK1 in the antidepressant-like effects of oleanolic acid in depression-like mice induced by long term corticosterone (CORT) injection. Behaviors, SGK1, brain-derived neurotrophic factor (BDNF) and its downstream targets were assessed after administration with oleanolic for three weeks. The results indicated that oleanolic acid increased the sucrose preference and decreased the immobility time. In addition, oleanolic acid decreased SGK1 and activated BDNF-AKT/mTOR signaling in the hippocampus of CORT-induced animals. However, we found that GSK650394, an inhibitor of SGK1 did not exert any effects on the behaviors, GR levels and BDNF signaling. The number of spines in hippocampal neurons was not changed by GSK650394 as well. Taken together, this study demonstrated that oleanolic acid produced the antidepressant-like effects, which might be related to the down-regulation of SGK1. However, inhibition of SGK1 directly lacks the effects in the treatment of depression.