BACKGROUND AND PURPOSEGinsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACHThe effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTSGinsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONSOur results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis.

Depression is a neuropsychiatric disorder accompanied by a decrease in the brain-derived neurotrophic factor (BDNF) signalling cascade in the hippocampus. Fenofibrate is a selective agonist of PPAR-α. In this study, we investigated the antidepressant-like effects of fenofibrate in C57BL/6J mice. EXPERIMENTAL APPROACHThe antidepressant-like effects of fenofibrate were first identified in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model. The changes in the hippocampal BDNF signalling pathway and adult hippocampal neurogenesis after CSDS and fenofibrate treatment were further investigated. A PPAR-α inhibitor, cannabinoid system inhibitors and BDNF signalling inhibitors were also used to determine the antidepressant mechanisms of fenofibrate. KEY RESULTSFenofibrate administration exhibited antidepressant-like effects in the FST and TST without affecting the locomotor activity of mice. Chronic fenofibrate treatment also prevented the depressive-like symptoms induced by CSDS. Moreover, fenofibrate restored the CSDS-induced decrease in the hippocampal BDNF signalling cascade and adult hippocampal neurogenesis. The antidepressant-like effects of fenofibrate could be blocked by a PPAR-α inhibitor and BDNF signalling inhibitors. CONCLUSIONS AND IMPLICATIONSTaken together, these results suggest that fenofibrate has antidepressant-like effects mediated through the promotion of the hippocampal BDNF signalling cascade. AbbreviationsBDNF, brain-derived neurotrophic factor; BrdU, 5-bromo-2-deoxyuridine; CREB, cAMP response element-binding protein;

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