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Biomolecules 2016, 6(4), 43; doi:10.3390/biom6040043

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

1
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
2
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
3
Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
4
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
5
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
6
Department of Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Natalia Osna
Received: 15 September 2016 / Revised: 23 October 2016 / Accepted: 28 October 2016 / Published: 9 November 2016
(This article belongs to the Collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
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Abstract

Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13–14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation) were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs) to ethanol (EtOH) and HIV trans-activator of transcription (Tat) protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits. View Full-Text
Keywords: SIV; alcohol; macaque; hippocampus; neural progenitor cells; Tat; microarray; neuroinflammation; neurogenesis SIV; alcohol; macaque; hippocampus; neural progenitor cells; Tat; microarray; neuroinflammation; neurogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Maxi, J.K.; Dean, M.; Zabaleta, J.; Reiss, K.; Bagby, G.J.; Nelson, S.; Winsauer, P.J.; Peruzzi, F.; Molina, P.E. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques. Biomolecules 2016, 6, 43.

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