Differential regulation of tachykinin and opioid system gene expression in brain and immune cells of chronic binge alcohol-treated, simian immunodeficiency virus (SIV)-infected macaques.

People living with HIV (PLWH) have a high likelihood of at-risk alcohol use and are at increased risk for neurocognitive decline. The underlying mechanisms involved in HIV-associated neurocognitive disorder (HAND) are not completely understood. Previously, we showed that chronic binge alcohol (CBA) administration produced behavioral deficits in non-antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)-infected macaques. Moreover, we observed that CBA/SIV enhanced neuroinflammatory gene expression and attenuated growth factor signaling in the frontal cortex (FC) and basal ganglia, effects that were partially ameliorated by ART. We hypothesized that the neuroinflammatory and growth factor changes observed could be associated with alterations in opioid, tachykinin, and endocannabinoid gene expression. Furthermore, that gene expression patterns in peripheral blood mononuclear cells (PBMCs) could serve as an indicators of expression changes in the brain (FC). We examined gene expression patterns of opioid, tachykinin, and endocannabinoid systems in FC and PBMCs isolated from CBA/SIV macaques. Expression of targeted genes as determined by RT-qPCR was analyzed in relation to CBA, ART, plasma, and brain viral loads (PVL and BVL, respectively) and compared to baseline (PBMC) or FC from SIV- controls. Results did not reveal parallel changes (in magnitude or direction) in PBMC and FC gene expression. FC expression of ORM1, POMC, and TACR1 were negatively associated with PVL (p=0.03, 0.002, 0.05 respectively). FC expression of TAC1 was positively associated with CBA exposure (p=0.05). PBMC expression of DAGLA was positively associated with CBA exposure; but negatively associated with combined CBA/ART exposure (p=0.03). Our findings reflect the complex interactions of SIV, CBA, and ART in modulating opioid and tachykinin system gene expression. Further studies are warranted to determine the relevance of these transcriptional changes in modulating HAND-related behaviors resulting from at-risk alcohol use and HIV/SIV exposure.