Brain Damage and Exercise Neurorestoration After Repeated Binge Alcohol Exposure

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DESCRIPTION (provided by applicant): The objective of this proposal is to evaluate cumulative brain damage and the potential for exercise neurorestoration in a rat model of an alcohol use disorder (AUD), which conforms to NIAAA's mission to improve the treatment of AUDs. Binge alcohol consumption impairs cognition and damages the brain by promoting cell death and inhibiting neurogenesis. Exercise, on the other hand, enhances brain health and function. Because binge drinking is a pattern of consumption, and thus by definition occurs repeatedly, this proposal will determine whether exercise can restore the brain after repeated binge episodes. Evidence suggests that repair attempts occur in the brain after a single binge. It is possible that if successive binges occur during ongoing repair attempts, they will not only independently cause damage, but also suppress efforts to repair damage caused by the previous binge. Our proposed experiments will test this hypothesis by timing subsequent binges to overlap with brain repair attempts, and quantify cumulative damage and resulting cognitive impairment. We will assess cognitive impairment both early and chronically after the last binge. We hypothesize that cognitive dysfunction will become more severe and more lasting with increasing binge episodes. Finally, we will determine whether post-binge exercise can ameliorate cumulative brain damage and cognitive dysfunction by allowing abstinent rats to exercise post-binge. We have previously shown that exercise is neuroprotective against damage incurred by a subsequent binge episode. We hypothesize that post-binge exercise will enhance natural brain repair processes during abstinence, resulting in reduced cognitive dysfunction compared to sedentary binge-exposed animals. This application is relevant to public health because it will determine whether exercise could be a useful component of treatment programs aimed at reducing the negative neural and functional consequences of binge alcohol consumption.