Chronic Binge Alcohol Administration in Simian Immunodeficiency Virus‐Infected Rhesus Macaques Modulates Pre‐Frontal Cortex Expression of Brain‐Derived Neurotrophic Factor and Microtubule‐Associated Protein 2

Abstract

Persons living with HIV/AIDS have a higher incidence of alcohol use and abuse. Previous studies by our group revealed that chronic binge alcohol (CBA) administration unmasks cognitive deficits in SIV-infected rhesus macaques. Chronic alcohol abuse and HIV infection result in loss of neurotrophic factors and neurons. We hypothesized that CBA administration would synergize with SIV to produce greater suppression of neurotrophic factor expression compared to SUC/SIV. Rhesus macaques were fitted with an intra-gastric catheter for delivery of alcohol (CBA, n = 7) or isocaloric sucrose (SUC, n = 7) for the duration of the experiment. Macaques were infected with SIVmac251 three months after initiation of CBA or SUC, one SUC animal was not infected. Macaques were euthanized when end-stage criteria were met (∼4 or 18 months post-inoculation), brains were excised and dissected. Pre-frontal cortex (PFC), caudate (Cd) and hippocampus (Hp) were used for analysis of tissue viral load and gene expression of BDNF and MAP2. Viral load was not significantly different in CBA animals or between brain regions. PFC was the only brain in which viral load was above the limit of detection in all animals. BDNF expression was lower in CBA/SIV only in the PFC (p=NS). MAP2 expression was lower in PFC and Cd (p=NS). Gene expression of MAP2 was positively correlated with BDNF in the PFC (p<0.01), Cd (p<0.01) and Hp (p=0.03). The results suggest that the PFC is most susceptible to combined SIV and CBA insult. Supported by AA07577, AA09803, AA11290.