Resveratrol counteracts lipopolysaccharide-induced depressive-like behaviors via enhanced hippocampal neurogenesis.

Liang Liu,Dan Yu,Qingwu Yang,Xiaotang Fan,Yulong Cai,Qin Zhang,Dayu Sun,Xie He,Haiwei Xu,Lian Wang,Xiaoyi Xiong,Xin Li

doi:10.18632/oncotarget.11178

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-κB 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.

Highlights

Depression is a chronic, recurring, and lifethreatening mood disorder, which affects more than 14 percent of the population and imposes a tremendous burden on both individuals and society [1]
The anti-depressant activities of RSV in the present experiments do not appear to be the result of an overall attenuation of psychomotor activity, as locomotor activity was unaffected by RSV treatment
We observed RSV pretreatment decreased Iba-1 labeling of microglia in the subgranular zone (SGZ) elicited by LPS, which may be partially responsible for the observed anti-depressant activity

Summary

Introduction

Depression is a chronic, recurring, and lifethreatening mood disorder, which affects more than 14 percent of the population and imposes a tremendous burden on both individuals and society [1]. A recent study by Fava et al found that a novel neurogenic compound, NSI-189, effectively treated major depressive disorder [9] These findings indicated that reduced adult hippocampal neurogenesis may be involved in the pathological mechanisms of depression and that up-regulating neurogenesis is a potential therapeutic target for treating depression. An LPS induced stress-based depressive mouse model [6, 22, 23] was used to test the antidepressant effects of RSV. We present the first demonstration that RSV activation of Sirt reverses the LPS-induced reductions in the number of RGL progenitor cells in the SGZ by stimulating symmetric division.

Results

Discussion

Conflicts of Interest