Resveratrol improves ovariectomy and chronic restraint stress-induced depression-like behaviors in mice through brain-derived neurotrophic factor associated structural synaptic remodeling.

Previous studies have shown that resveratrol has antidepressant effects in a variety of depression models, but the effect and mechanism of resveratrol on menopausal depression are unclear. In this study, transgenic mice were ovariectomized combined with chronic restraint stress to establish a model of menopausal depression. The antidepressant effect of resveratrol was evaluated by tail suspension test (TST), forced swimming test, sucrose preference test (SPT), and novel inhibition feeding test (NSFT). Using the characteristic expression of yellow fluorescent protein in excitatory neurons of transgenic mice, the effects of resveratrol on the density of dendrites and dendritic spines were evaluated by a three-dimensional imaging technique. Brain-derived neurotrophic factor (BDNF), cofilin1, and p-cofilin1 were quantitatively analyzed by quantitative PCR and immunofluorescence quantification to explore the effects of resveratrol on synaptic plasticity in the hippocampus and medial prefrontal cortex (mPFC) and its mechanism. The results revealed that resveratrol significantly decreased the immobility time in TST, shortened the feeding latency and increased the food intake in NSFT, and enhanced the sucrose consumption in SPT. Consistent with these changes, resveratrol treatment significantly increased the density of p-cofilin1 immunoreactive dendritic spines and the mRNA level of BDNF in these brain regions. The results suggest that resveratrol can improve the synaptic plasticity in the corresponding brain regions by upregulating BDNF levels, enhancing the phosphorylation of cofilin 1, increasing the density of dendrites and dendritic spines in the hippocampus and mPFC, and ultimately improving menopausal depression-like behaviors.