Resveratrol counteracts lipopolysaccharide-induced depressive-like behaviors<i>via</i>enhanced hippocampal neurogenesis

Abstract

// Liang Liu 1,2 , Qin Zhang 1 , Yulong Cai 1 , Dayu Sun 1,2 , Xie He 1 , Lian Wang 1 , Dan Yu 1 , Xin Li 1 , Xiaoyi Xiong 2 , Haiwei Xu 3 , Qingwu Yang 2 and Xiaotang Fan 1 1 Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China 2 Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, China 3 Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing, PR China Correspondence to: Xiaotang Fan, email: // Qingwu Yang, email: // Keywords : resveratrol; depression; neurogenesis; LPS; radial glial cells; Pathology Section Received : May 26, 2016 Accepted : July 20, 2016 Published : August 10, 2016 Abstract Radial glial-like cells (RGLs) in the adult dentate gyrus (DG) function as progenitor cells for adult hippocampal neurogenesis, a process involved in the stress-related pathophysiology and treatment efficiency of depression. Resveratrol (RSV) has been demonstrated to be a potent activator of neurogenesis. The present study investigated whether chronic RSV treatment has antidepressant potential in relation to hippocampal neurogenesis. Mice received two weeks of RSV (20 mg/kg) or dimethylsulfoxide (DMSO) treatment, followed by lipopolysaccharide (LPS; 1 mg/kg) or saline injections for 5 days. We found that RSV treatment abrogated the increased immobility in the forced swimming test and tail suspension test induced by LPS. Immunohistochemical staining revealed that RSV treatment reversed the increase in microglial activation and the inhibition in DG neurogenesis. RSV treatment also attenuated LPS-induced defects in the expanding of RGLs through promoting symmetric division. In addition, RSV ameliorated LPS-induced NF-&kappa;B activation in the hippocampus coincides with the up-regulation levels of Sirt1 and Hes1. Taken together, these data indicated that RSV-induced Sirt1 activation counteracts LPS-induced depression-like behaviors via a neurogenic mechanism. A new model to understand the role of RSV in treating depression may result from these findings.