Resveratrol modulates response against acute inflammatory stimuli in aged mouse brain

Exp Gerontol. 2018 Feb:102:3-11. doi: 10.1016/j.exger.2017.11.014. Epub 2017 Nov 24.

Abstract

With upcoming age, the capability to fight against harmful stimuli decreases and the organism becomes more susceptible to infections and diseases. Here, the objective was to demonstrate the effect of dietary resveratrol in aged mice in potentiating brain defenses against LipoPolySaccharide (LPS). Acute LPS injection induced a strong proinflammatory effect in 24-months-old C57/BL6 mice hippocampi, increasing InterLeukin (Il)-6, Tumor Necrosis Factor-alpha (Tnf-α), Il-1β, and C-X-C motif chemokine (Cxcl10) gene expression levels. Resveratrol induced higher expression in those cytokines regarding to LPS. Oxidative Stress (OS) markers showed not significant changes after LPS or resveratrol, although for resveratrol treated groups a slight increment in most of the parameters studies was observed, reaching signification for NF-kB protein levels and iNOS expression. However, Endoplasmic Reticulum (ER) stress markers demonstrated significant changes in resveratrol-treated mice after LPS treatment, specifically in eIF2α, BIP, and ATF4. Moreover, as described, resveratrol is able to inhibit the mechanistic Target of Rapamycin (mTOR) pathway and this effect could be linked to (eIF2α) phosphorylation and the increase in the expression of the previously mentioned proinflammatory genes as a response to LPS treatment in aged animals. In conclusion, resveratrol treatment induced a different cellular response in aged animals when they encountered acute inflammatory stimuli.

Keywords: Aging; Cytokines; Inflammation; eukaryotic Initiation Factor 2 (eIF2); iNOS; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects
  • Eukaryotic Initiation Factor-2B / metabolism
  • Gene Expression Regulation
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism*
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Eukaryotic Initiation Factor-2B
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • lipopolysaccharide, Escherichia coli O111 B4
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • Resveratrol