Effects of chronic and binge ethanol administration on mouse cerebellar and hippocampal neuroinflammation

ABSTRACT

Background: Hippocampal and cerebellar neuropathology occurs in individuals with alcohol use disorders (AUD), resulting in impaired cognitive and motor function.

Objectives: Evaluate the effects of ethanol on the expression of pro- and anti-inflammatory molecules, as well as the effects of the anti-inflammatory PPAR-γ agonist pioglitazone in suppressing ethanol-induced neuroinflammation.

Methods: Adult male and female mice were treated chronically with ethanol for just under a month followed by a single acute binge dose of ethanol. Animals were provided liquid diet in the absence of ethanol (Control; n = 18, 9 M/9F), liquid diet containing ethanol (ethanol; n = 22, 11 M/11F), or liquid diet containing ethanol plus gavage administration of 30.0 mg/kg pioglitazone (ethanol + pioglitazone; n = 20, 10 M/10F). The hippocampus and cerebellum were isolated 24 h following the binge dose of ethanol, mRNA was isolated, and pro- and anti-inflammatory molecules were quantified by qRT-PCR.

Results: Ethanol significantly (p < .05) increased the expression of pro-inflammatory molecules IL-1β, TNF-α, CCL2, and COX2; increased the expression of inflammasome-related molecules NLRP3 and Casp1 but decreased IL-18; and altered the expression of anti-inflammatory molecules including TGFβR1 in the hippocampus and cerebellum, though some differences were observed between males and females and the two brain regions. The anti-inflammatory pioglitazone inhibited ethanol-induced alterations in the expression of most, but not all, inflammation-related molecules.

Conclusion: Chronic plus binge administration of ethanol induced the expression of inflammatory molecules in adult mice and pioglitazone suppressed ethanol-induced neuroinflammation.

KEYWORDS:

• Hippocampus
• cerebellum
• ethanol
• alcohol addiction
• inflammation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the National Institutes of Health: National Institute on Alcohol Abuse and Alcoholism under Grants [AA024695, AA026665, AA027111].