Resveratrol ameliorates estrogen deficiency-induced depression- and anxiety-like behaviors and hippocampal inflammation in mice

Abstract

Rationale: Resveratrol (RSV) has been indicated to exhibit beneficial effects on depression and anxiety treatment by suppression of inflammatory processes. Depression triggered by deficiency of estrogen and anxiety-like behaviors are associated with inflammation. The role of RSV in ovariectomized mice is unclear.

Objectives: We examine whether the RSV, a Sirt1 activator, alleviates ovariectomy-induced anxiety- and depression-like behaviors through the inhibition of inflammatory processes.

Methods: Female C57BL/6J mice (6-8 weeks of age, 17-20 g) were ovariectomized and treated with RSV at a dose of 20 mg/kg for 2 weeks. Depression- and anxiety-like behaviors were compared with vehicle-injected control animals. Immunohistochemistry and qPCR were used to detect inflammation in the hippocampal region.

Results: Ovariectomized mice were observed to suffer from anxiety- and depression-like behaviors. These effects were attenuated by treatment with RSV. Immunohistochemical staining results showed that RSV could reverse the increase of microglial activation in the hippocampal dentate gyrus. At a molecular level, RSV inhibited the activation of NLRP3 and NF-κB in the hippocampal region caused by deficiency of estrogen.

Conclusions: RSV suppressed the production of inflammatory cytokines by enhancing Sirt1 levels. Our findings indicated that RSV-induced Sirt1 activation counteracted estrogen deficiency-induced psychobehavioral changes via inhibition of inflammatory processes in the hippocampus. In anxiety and depression disorders, RSV is supposed to be an effective treatment for postmenopausal changes.

Keywords: Anxiety; Depression; Inflammation; Ovariectomy; Resveratrol.