Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques.
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.
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. jmaxi@lsuhsc.edu.
John K
JK
Maxi
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. mdean3@lsuhsc.edu.
Matt
M
Dean
Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. jzabal@lsuhsc.edu.
Jovanny
J
Zabaleta
Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. kreiss@lsuhsc.edu.
Krzysztof
K
Reiss
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. gbagby@lsuhsc.edu.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. gbagby@lsuhsc.edu.
Gregory J
GJ
Bagby
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. snelso1@lsuhsc.edu.
Steve
S
Nelson
Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pwinsa@lsuhsc.edu.|Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pwinsa@lsuhsc.edu.
Peter J
PJ
Winsauer
Department of Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. fperuz@lsuhsc.edu.
Francesca
F
Peruzzi
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pmolin@lsuhsc.edu.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. pmolin@lsuhsc.edu.
Patricia E
PE
Molina
D000818:Animals; D063425:Binge Drinking / Q000150:complications* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000009:adverse effects; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000276:immunology*; D008253:Macaca mulatta / Q000821:virology; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology
D000431:Ethanol
SIV; Tat; alcohol; hippocampus; macaque; microarray; neural progenitor cells; neurogenesis; neuroinflammation