Brain Damage and Exercise Neurorestoration After Repeated Binge Alcohol Exposure

描述（由申请人提供）：本提案的目的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潜力，这符合NIAAA改善AUD治疗的使命。酗酒会损害认知能力，并通过促进细胞死亡和抑制神经发生来损害大脑。另一方面，锻炼可以增强大脑的健康和功能。由于狂饮是一种消费模式，因此从定义上看，它是反复发生的，这项提议将确定运动是否能在反复狂饮后恢复大脑。有证据表明，在一次暴食之后，大脑会进行修复尝试。如果连续的暴食发生在正在进行的修复尝试中，它们不仅会独立地造成损害，而且还会抑制修复前一次暴食造成的损害的努力。我们提出的实验将通过确定随后的狂欢与大脑修复尝试重叠的时间来验证这一假设，并量化累积损伤和由此导致的认知损伤。我们将在最后一次暴食后早期和长期评估认知损伤。我们假设，随着暴食发作次数的增加，认知功能障碍会变得更严重、更持久。最后，我们将通过让戒断的大鼠在暴食后运动来确定暴食后运动是否可以改善累积的脑损伤和认知功能障碍。我们之前已经证明，运动可以保护神经免受随后的暴饮暴食造成的损害。我们假设暴饮暴食后的运动将增强禁欲期间的自然大脑修复过程，与久坐不动的暴饮暴食暴露的动物相比，导致认知功能障碍减少。这项应用与公众健康相关，因为它将决定运动是否可以成为旨在减少酗酒对神经和功能的负面影响的治疗方案的有用组成部分。

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. PUBLIC HEALTH RELEVANCE: This application is relevant to public health because it will determine the effects of exercise on brain and behavior in a model of binge alcohol consumption. Binge drinking causes brain damage and cognitive dysfunction and increases the risk of dementia later in life. Given that binge drinking is common in the United States, there is significant need to develop effective treatments to ameliorate binge-induced brain injury and cognitive impairments.