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

•Hybrid model combining intragastric ethanol feeding and high fat diet in mice•Increased pro-inflammatory markers and glia activation in Hybrid•Reduced neuronal marker NeuN levels in ethanol-sensitive brain regions in Hybrid•Increased P2X7R levels in ethanol-sensitive brain regions in Hybrid•Contribution of high fat diet to the increase in P2X7R expression and glia activation.

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.