Resveratrol Rescues the Impairments of Hippocampal Neurons Stimulated by Microglial Over-Activation In Vitro

Cell Mol Neurobiol. 2015 Oct;35(7):1003-15. doi: 10.1007/s10571-015-0195-5. Epub 2015 Apr 22.

Abstract

Resveratrol is a naturally occurring phytoalexin found in red grapes, and believed to have neuroprotective, anti-oxidant, and anti-inflammatory effects. But little is known about its effect on the neural impairments induced by microglial over-activation, which leads to neuroinflammation and multiple pathophysiological damages. In this study, we aimed to investigate the protective effects of resveratrol on the impairments of neural development by microglial over-activation insult. The results indicated that resveratrol inhibited the lipopolysaccharide (LPS)-dependent release of cytokines from activated microglia and LPS-dependent changes in NF-κB signaling pathway. Conditioned medium (CM) from activated microglia treated by resveratrol directly protected primary cultured hippocampal neurons against LPS-CM-induced neuronal death, and restored the inhibitory effects of LPS-CM on dendrite sprouting and outgrowth. Finally, neurons cultured in CM from LPS-stimulated microglia treated by resveratrol exhibited increased spine density compared to those without resveratrol treatment. Our findings support that resveratrol inhibits microglial over-activation and alleviates neuronal injuries induced by microglial activation. Our study suggests the use of resveratrol as an alternative intervention approach that could prevent further neuronal insults.

Keywords: Hippocampal neuron; LPS; Microglia; NF-κB; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Lipopolysaccharides / toxicity
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Resveratrol
  • Stilbenes / pharmacology*

Substances

  • Lipopolysaccharides
  • Neuroprotective Agents
  • Stilbenes
  • Resveratrol