Resveratrol alleviates ethanol-induced neuroinflammation in vivo and in vitro: Involvement of TLR2-MyD88-NF-κB pathway

Int J Biochem Cell Biol. 2018 Oct;103:56-64. doi: 10.1016/j.biocel.2018.07.007. Epub 2018 Aug 11.

Abstract

Excessive ethanol (EtOH) intake affects cognitive function and leads to permanent learning and memory deficits. EtOH-induced neuroinflammation plays an important role in EtOH neurotoxicity. Studies have shown that EtOH activates microglia and induces an inflammatory response. Resveratrol (Rsv) is a natural polyphenol found in a wide variety of plants and fruits, and produces the neuroprotective and anti-inflammatory effects in the central nervous system. However, effect of Rsv on EtOH-induced neuroinflammation is still unknown. We investigated the anti-inflammatory effect of Rsv in the context of EtOH-induced neurotoxicity and the molecular mechanisms potentially involved in the effect. The results showed that treatment of rats with Rsv prevented the deficits of spatial reference memory induced by EtOH and mitigated EtOH-induced neuroinflammation by inhibiting microglial activation and decreasing the levels of inflammatory cytokines including interleukin-1β, interleukin-6 and tumor necrosis factor α. The further studies indicated that Rsv reduced TLR2 expression in vivo and in vitro, and downregulated expression of myeloid differentiation primary response 88 (MyD88) and phosphorylation of nuclear factor κB (NF-κB). These data demonstrate that Rsv alleviates the ethanol-induced neuroinflammation via inhibition of TLR2-MyD88-NF-κB signal pathway.

Keywords: Ethanol; Microglia; Nuclear factor κB; Resveratrol; TLR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Diseases* / chemically induced
  • Central Nervous System Diseases* / drug therapy
  • Central Nervous System Diseases* / metabolism
  • Ethanol / adverse effects*
  • Ethanol / pharmacology
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism
  • Myeloid Differentiation Factor 88 / metabolism*
  • NF-kappa B / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Neuroprotective Agents
  • Tlr2 protein, rat
  • Toll-Like Receptor 2
  • Ethanol
  • Resveratrol