Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior

Physiol Behav. 2017 Dec 1;182:54-61. doi: 10.1016/j.physbeh.2017.09.024. Epub 2017 Sep 28.


Growing evidence suggests that inflammatory processes may be involved in depressive disorders. Inflammation is known to induce mitochondrial dysfunction in the nervous system. However, whether mitochondrial dysfunction is involved in the occurrence of inflammation-induced depressive-like behavior remains to be investigated. The present study aims to firstly, clarify whether mitochondrial dysfunction contributes to lipopolysaccharide (LPS)-induced depression-like behavior in mice and secondly, determine whether the anti-oxidant resveratrol alleviates inflammation-induced depressive-like behavior through the prevention of mitochondrial dysfunction in the hippocampus. We found that the administration of LPS led to mitochondrial oxidative stress and dysfunction as evidenced by increased mitochondrial superoxide production and decreased mitochondrial membrane potential and ATP production in the hippocampus. These effects were attenuated by intracerebroventricular (ICV) Injection of the mitochondria-targeted antioxidant Mito-TEMPO. LPS-treated mice displayed depressive-like behaviors as evidenced by reduced sucrose preference, increased immobility time and decreased struggling time in the forced swimming test. Both Mito-TEMPO and resveratrol could significantly improve the LPS-induced depressive-like behaviors. In contrast, ICV Injection of rotenone, the mitochondrial respiratory chain inhibitor, induced mitochondrial oxidative stress and dysfunction in the hippocampus, and resulted in depressive-like behaviors. Moreover, resveratrol alleviated the LPS-induced apoptosis of hippocampal cells. The antidepressant action of resveratrol was accomplished through the interruption of mitochondrial oxidative stress and the prevention of cell apoptosis in the hippocampus. These findings support the potential for resveratrol as a possible pharmacological agent for depression treatment in the future.

Keywords: Depression-like behavior; Hippocampus; Lipopolysaccharide; Mitochondrial dysfunction; Resveratrol.

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cyclic N-Oxides / pharmacology
  • Depression / etiology
  • Depression / prevention & control*
  • Disease Models, Animal
  • Food Preferences / drug effects
  • Hippocampus / drug effects
  • Hippocampus / ultrastructure*
  • Inflammation / chemically induced
  • Inflammation / complications
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Resveratrol
  • Rotenone / pharmacology
  • Stilbenes / therapeutic use*
  • Swimming
  • Uncoupling Agents / pharmacology


  • Antidepressive Agents
  • Antioxidants
  • Cyclic N-Oxides
  • Stilbenes
  • Uncoupling Agents
  • Rotenone
  • Resveratrol