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

Biomolecules. 2016 Nov 9;6(4):43. doi: 10.3390/biom6040043.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binge Drinking / complications*
  • Binge Drinking / genetics
  • Binge Drinking / immunology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Ethanol / adverse effects
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation / drug effects
  • Hippocampus / immunology*
  • Macaca mulatta / virology
  • Mice
  • Neurogenesis / drug effects
  • Simian Acquired Immunodeficiency Syndrome / genetics*
  • Simian Acquired Immunodeficiency Syndrome / immunology


  • Ethanol