Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques.
Biomolecules
; 6(4)2016 11 09.
Article
em En
| MEDLINE
| ID: mdl-27834864
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 ßIII 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.
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Imunodeficiência Adquirida dos Símios
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Perfilação da Expressão Gênica
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Consumo Excessivo de Bebidas Alcoólicas
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Hipocampo
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article