Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques
| Autor: | Matt Dean, Gregory J. Bagby, Peter J. Winsauer, John K. Maxi, Jovanny Zabaleta, Patricia E. Molina, Francesca Peruzzi, Krzysztof Reiss, Steve Nelson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
hippocampus viruses Neurogenesis lcsh:QR1-502 Simian Acquired Immunodeficiency Syndrome Inflammation neural progenitor cells Hippocampal formation medicine.disease_cause Biochemistry Macaque lcsh:Microbiology Article Binge Drinking neuroinflammation 03 medical and health sciences Mice 0302 clinical medicine Immune system Immunity biology.animal medicine Animals Molecular Biology Neuroinflammation Cells Cultured biology Ethanol alcohol Gene Expression Profiling macaque virus diseases Cell Differentiation Simian immunodeficiency virus Virology Macaca mulatta 3. Good health 030104 developmental biology Gene Expression Regulation SIV Immunology Tat microarray neurogenesis medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Biomolecules Biomolecules, Vol 6, Iss 4, p 43 (2016) Biomolecules; Volume 6; Issue 4; Pages: 43 |
| ISSN: | 2218-273X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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