Effects of ethanol concentration in binge drinking during HIV-1 infection

描述(由申请人提供)：这是一份F31国家研究服务奖(NRSA)重新提交的申请。拟议的项目将使我为成为一名独立研究员和伦理科学家做好准备。这项拟议研究的重点是调查在年轻人中非常常见的定期酗酒是否具有乙醇(Etoh)浓度依赖的影响，特别是在感染HIV-1期间。酗酒是18-25岁年轻人中一种常见的酒精滥用形式。年轻人通常倾向于在派对和宿舍里狂饮，相当多的人(43.8%)更喜欢烈酒。酒精饮料的乙醇或酒精体积(ABV)含量差别很大，从5%的低ABV到40%或更高的高。大量饮用高ABV饮料会损害年轻人群的学习和认知。酗酒与HIV-1感染之间有很高的相关性。酗酒不仅是接触艾滋病毒感染的高危因素，而且与年轻人在工作记忆和额叶处理方面的神经认知缺陷有关。因此，在存在艾滋病毒感染的情况下酗酒，这也是以神经认知障碍为特征的，如艾滋病毒-1相关性痴呆(HAD)，可能会对学习和认知缺陷产生附加影响。目前，很少有研究研究酒精消费中乙醇的相对浓度是否与非疾病和疾病条件(如HIV-1感染)中酒精介导的细胞和分子变化相关。我们假设，在HIV-1病毒和免疫相关基因的表达上存在ABV依赖的影响，这些基因可以导致不同的生理和行为问题，特别是在学习和认知能力方面。我们将使用HIV-1转基因(HIV-1TG)大鼠，这是一种与高效抗逆转录病毒治疗(HAART)中的HIV-1感染者具有相似特征的非传染性啮齿动物模型，以探讨乙醇对脑内HIV-1病毒和免疫相关基因表达的ABV依赖效应。将使用实时聚合酶链式反应和聚合酶链式反应阵列分析等技术。我们还将使用改进的Morris水迷宫测试进行行为分析，以确定ABV依赖的分子改变与行为之间是否存在相关性。有了F31 NRSA奖学金，我将能够获得各种研究方法的经验，包括分子技术、动物处理和行为分析，以及负责任的研究行为，以成功完成拟议的项目，并为自己最终发展成为一名独立的、有道德的科学家做好准备。

DESCRIPTION (provided by applicant): This is an F31 National Research Service Award (NRSA) resubmission application. The proposed project will prepare me to become an independent researcher and an ethical scientist. The focus of the proposed study is to investigate whether regular binge alcohol abuse, which is very common in the young population, has ethanol (EtOH) concentration-dependent effects, particularly during HIV-1 infection. Binge drinking is a common form of alcohol abuse in the young population between 18-25 years of age. Young people generally tend to binge drink at parties and in dormitories and a significant number (43.8%) prefer hard liquor. Alcoholic beverages differ widely in their EtOH or alcohol by volume (ABV) content, ranging from a low of 5% ABV to a high of 40% or greater. Binge drinking of high ABV beverages can damage learning and cognition in the young population. There is a high correlation between alcohol abuse and HIV-1 infection. Alcohol abuse is not only a high risk factor for exposure to HIV infection, but has also been correlated with neurocognitive deficits in working memory and frontal lobe processing in the young population. Therefore, alcohol abuse in the presence of HIV infection, which is also characterized by neurocognitive disorders, such as HIV-1 associated dementia (HAD), can have an additive effect on learning and cognitive deficits. At present, there are few studies examining whether the relative concentration of EtOH in the alcohol consumed correlates with alcohol-mediated cellular and molecular changes in non-disease and disease conditions such as HIV-1 infection. We hypothesize that there are ABV-dependent effects on the expression of HIV-1 viral and immune-related genes that can cause different physiological and behavioral problems, particularly in learning and cognitive abilities. We will use the HIV-1 transgenic (HIV-1Tg) rat, a non-infectious rodent model with similar characteristics as HIV-1 infected people on Highly Active Anti-Retroviral Therapy (HAART), to investigate the ABV-dependent effects of EtOH on HIV-1 viral and immune-related gene expression in the brain. Techniques such as real-time PCR and PCR array analysis will be used. We will also perform behavioral analysis using a modified Morris water maze test to determine if there is a correlation between ABV-dependent molecular alterations and behavior. With the F31 NRSA fellowship award, I will be able to acquire experience in a wide variety of research methods, including molecular techniques, animal handling, and behavior analysis, and responsible conduct of research to successfully complete the proposed project and to prepare myself to eventually develop into an independent and ethical scientist.