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.
Alcoholic beverages differ widely in their ethanol (EtOH) content (alcohol by volume, ABV), ranging from as low as 5% (beer) to 40% or higher (hard liquor). Binge drinking, which is a high risk factor for exposure to HIV-1 infection, is prevalent n the young population in the United States, and young people tend to consume hard liquor. Since both alcohol abuse and HIV-1 infection can cause neurocognitive deficits, the studies proposed can provide valuable molecular and behavioral information on the effects of binge drinking of high EtOH concentration beverages, particularly in relation to learning and cognitive deficits that will be clinically relevant for the prevention and management of HIV-1 infection in young individuals prone to binge alcohol abuse.