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Biomolecules. 2016 Nov 9;6(4). pii: E43.

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

Author information

1
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. jmaxi@lsuhsc.edu.
2
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. mdean3@lsuhsc.edu.
3
Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. jzabal@lsuhsc.edu.
4
Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. kreiss@lsuhsc.edu.
5
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. gbagby@lsuhsc.edu.
6
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. gbagby@lsuhsc.edu.
7
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. snelso1@lsuhsc.edu.
8
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pwinsa@lsuhsc.edu.
9
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pwinsa@lsuhsc.edu.
10
Department of Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. fperuz@lsuhsc.edu.
11
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pmolin@lsuhsc.edu.
12
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pmolin@lsuhsc.edu.

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.

KEYWORDS:

SIV; Tat; alcohol; hippocampus; macaque; microarray; neural progenitor cells; neurogenesis; neuroinflammation

PMID:
27834864
PMCID:
PMC5197953
DOI:
10.3390/biom6040043
[Indexed for MEDLINE]
Free PMC Article

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