Chronic ethanol exposure combined with high fat diet up-regulates P2X7 receptors that parallels neuroinflammation and neuronal loss in C57BL/6J mice

J Neuroimmunol. 2015 Aug 15:285:169-79. doi: 10.1016/j.jneuroim.2015.06.007. Epub 2015 Jun 20.

Abstract

The present investigation tested the role of ATP-activated P2X7 receptors (P2X7Rs) in alcohol-induced brain damage using a model that combines intragastric (iG) ethanol feeding and high fat diet in C57BL/6J mice (Hybrid). The Hybrid paradigm caused increased levels of pro-inflammatory markers, changes in microglia and astrocytes, reduced levels of neuronal marker NeuN and increased P2X7R expression in ethanol-sensitive brain regions. Observed changes in P2X7R and NeuN expression were more pronounced in Hybrid paradigm with inclusion of additional weekly binges. In addition, high fat diet during Hybrid exposure aggravated the increase in P2X7R expression and activation of glial cells.

Keywords: Astrocytes; High fat diet; Intragastric ethanol feeding; Microglia; Neuroinflammation and neuronal loss; Pro-inflammatory cytokines; Purinergic P2X7 receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cell Count / methods
  • Diet, High-Fat / adverse effects*
  • Ethanol / administration & dosage*
  • Ethanol / toxicity
  • Inflammation Mediators / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Receptors, Purinergic P2X7 / biosynthesis*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*

Substances

  • Inflammation Mediators
  • Receptors, Purinergic P2X7
  • Ethanol