Abstract
The female brain appears selectively vulnerable to the neurotoxic effects of alcohol, but the reasons for this are unclear. One possibility is an exaggerated neuroimmune response in the female brain, such that alcohol increases microglia number and reactivity to subsequent stimuli, such as exercise. It is important to better characterize the interactive neural effects of alcohol and exercise, as exercise is increasingly being used in the treatment of alcohol use disorders. The present study compared the number of microglia and evidence of their activation in alcohol-vulnerable regions of the brain (medial prefrontal cortex and hippocampus) in male and female rats following binge alcohol and/or exercise. Binge alcohol increased microglia number and morphological characteristics consistent with their activation in the female brain but not the male, regardless of exercise. Binge alcohol followed by exercise did increase the number of MHC II+ (immunocompetent) microglia in females, although the vast majority of microglia did not express MHC II. These results indicate that binge alcohol exerts sex-specific effects on microglia that may result in enhanced reactivity to a subsequent challenge and in part underlie the apparent selective vulnerability of the female brain to alcohol.
Highlights
Research in the field of alcohol has historically focused on men, with women receiving comparably little representation, due to men having a higher risk for developing problematic drinking [1,2].the prevalence of alcohol use disorders (AUD) in young women is increasing [3,4]
We postulate that exercise may represent a secondary challenge, as we have previously found that 4 weeks of exercise after binge alcohol resulted in a drastic reduction in microglia number in the medial prefrontal cortex of female rats [40], in contrast to alcohol naïve animals that exercised, the latter of which showed an increase in mPFC microglia
There was a significant increase in microglia in binged females compared to males. These results indicate that binge alcohol selectively increased microglia number in the female hippocampus but decreased it in the male mPFC and hippocampus
Summary
Research in the field of alcohol has historically focused on men, with women receiving comparably little representation, due to men having a higher risk for developing problematic drinking [1,2].the prevalence of alcohol use disorders (AUD) in young women is increasing [3,4]. Using a 4-day binge model of alcohol-induced neurodegeneration, we have shown that female rats have a significant loss of dentate gyrus granule neurons that is not seen in males, as well as an acquisition deficit in learning the location of the platform in the Morris water maze [15]. This finding, coupled with findings from clinical populations, suggests that the female brain is vulnerable to the neurotoxic effects of alcohol in both rats and humans. The mechanisms underlying the apparent vulnerability of the female brain to the damaging effects of alcohol have not been established, sex differences in innate immunity may be a contributing factor
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