Brain Damage and Exercise Neurorestoration After Repeated Binge Alcohol Exposure

描述(申请人提供)：这项建议的目标是评估酒精使用障碍(AUD)大鼠模型的累积脑损伤和运动神经恢复的可能性，这符合NIAAA改进AUD治疗的使命。酗酒会通过促进细胞死亡和抑制神经发生来损害认知和大脑。另一方面，锻炼可以增强大脑的健康和功能。由于酗酒是一种消费模式，因此从定义上讲，酗酒是反复发生的，因此这项提议将决定运动是否能在反复酗酒后恢复大脑。有证据表明，修复尝试在一次狂欢之后发生在大脑中。有可能的是，如果在正在进行的修复尝试中出现连续的狂欢，它们不仅会独立地造成损害，而且还会抑制修复先前狂欢造成的损害的努力。我们提议的实验将通过将随后的狂欢与大脑修复尝试重叠来测试这一假设，并量化累积损伤和由此导致的认知损伤。我们将在最后一次狂欢之后对认知障碍进行早期和慢性评估。我们假设，随着狂欢发作的增加，认知功能障碍将变得更加严重和持久。最后，我们将确定暴饮暴食后的运动是否可以通过允许戒断大鼠在暴饮暴食后进行锻炼来改善累积的脑损伤和认知功能障碍。我们之前已经证明，锻炼对随后的狂欢发作造成的损害具有神经保护作用。我们假设，与久坐不动的暴饮暴食的动物相比，暴饮暴食后的运动将增强禁欲期间的自然大脑修复过程，导致认知功能障碍的减少。这项申请与公共健康相关，因为它将决定锻炼是否可以成为旨在减少酗酒带来的负面神经和功能后果的治疗计划的有用组成部分。

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.