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Alcohol, Exercise & the Female Brain

酒精、运动

基本信息

批准号：
10395480
负责人：
J. Leigh Leasure
金额：
$ 34.43万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10395480
关键词：
Address Affective Aging Alcohol consumption Alcohol-Induced Disorders Alcohols Behavior Control Brain Brain Diseases Brain Injuries Brain region Cell Death Cognition Cognitive Consumption Corticosterone Cytoplasmic Granules Data Development Elements Equilibrium Exercise Exposure to Female Gender Gliosis Glucocorticoid Receptor Glucocorticoids Gonadal Hormones Gonadal Steroid Hormones Health Heavy Drinking Hippocampus (Brain)Hormones Human Impairment Intervention Knowledge Laboratories Mediating Mineralocorticoid Receptor Modeling Nerve Degeneration Neurons Organ Ovarian hormone Pathway interactions Pattern Play Predisposition Public Health Rattus Receptor Activation Receptor Signaling Research Rodent Rodent Model Role Sex Differences Stress Stroke System Testing Testosterone United States Woman alcohol abuse therapy alcohol effect alcohol exposure alcohol use disorder antagonist base behavioral impairment brain repair clinically relevant drinking effective therapy experience experimental study functional disability hypothalamic-pituitary-adrenal axis improved male men negative affect neurogenesis neurorestoration novel physiologic stressor receptor binding repaired restoration sedentary sex treatment strategy way finding

项目摘要

Project Summary Alcohol use disorder (AUD) is a significant public health problem in the United States. Binge pattern consumption, the most common form of AUD, damages corticolimbic brain regions essential for cognition and behavioral control, including the hippocampus. Compared to men, women disproportionately experience alcohol-related health problems, including organ damage, and a growing body of research indicates that they are also more likely than men to suffer alcohol-induced brain damage. The apparent vulnerability of the female brain to alcohol necessitates a more thorough understanding of underlying mechanisms, to inform the development of effective treatment strategies. Our preliminary data from a rat model show sex-dependent effects of binge alcohol on the hippocampus and hippocampal-dependent cognition, with females significantly more negatively affected, and our proposed experiments will develop this model. The traditional suspects when investigating sex differences are gonadal hormones, either due to their permanent, organizational effects or their transient, activational (circulating) effects. Because circulating ovarian hormones are protective against other forms of brain injury, such as stroke, the vulnerability of the female brain to alcohol damage presents a conundrum. To resolve it, our proposed experiments will test the novel hypothesis that early organizational (but not circulating) sex hormone effects are responsible for the selective vulnerability of the female brain to binge alcohol exposure. Finally, although the female hippocampus may be selectively vulnerable to binge alcohol, we have also found that it can be repaired by exercise. We will use this model of exercise-driven repair to probe underlying mechanisms and address the novel question of whether the repaired hippocampus functions like the never-damaged hippocampus. Using a clinically-relevant rodent model, our three specific aims will 1) establish the selective vulnerability of the female brain to binge alcohol; 2) determine the contribution of organizational and/or circulating sex hormone effects and 3) pinpoint mechanisms and efficacy of exercise- driven restoration. Our findings will elucidate the mechanisms underlying female brain susceptibility to alcohol damage and inform the development of novel interventions to enhance brain repair.

项目摘要酒精使用障碍（AUD）是美国一个重要的公共卫生问题。狂欢模式消费，最常见的形式的AUD，损害皮质边缘脑区的认知和行为控制包括海马体与男性相比，酒精相关的健康问题，包括器官损伤，越来越多的研究表明，也比男性更容易遭受酒精引起的脑损伤。女性明显的脆弱性大脑对酒精的依赖需要更深入地了解潜在的机制，制定有效的治疗策略。我们对大鼠模型的初步数据显示，酗酒对海马和海马依赖性认知的影响，女性显著更多的负面影响，我们提出的实验将发展这个模型。传统的嫌疑犯，研究性别差异是性腺激素，无论是由于其永久性，组织的影响，其短暂的激活（循环）效应。因为循环中的卵巢激素可以保护其他形式的脑损伤，如中风，女性大脑对酒精损伤的脆弱性，难题为了解决这个问题，我们提出的实验将测试新的假设，即早期组织（但性激素的影响是女性大脑选择性地对暴食敏感的原因酒精暴露最后，尽管女性海马体可能选择性地易受酗酒的影响，也发现它可以通过锻炼来修复。我们将使用这种运动驱动修复模型来探索潜在的机制，并解决新的问题，是否修复海马功能一样，从未受损的海马体使用临床相关的啮齿动物模型，我们的三个具体目标将1）确定女性大脑对酗酒的选择性脆弱性; 2）确定组织和/或循环性激素的影响和3）精确的机制和锻炼的功效- 驱动恢复。我们的发现将阐明女性大脑对酒精敏感性的机制损伤，并为开发新的干预措施以增强大脑修复提供信息。