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Proteomic Analysis of Chronic Binge Alcohol-Induced Hippocampal and Anterior Cingulate Cortex Neuroadaptations in Simian Immunodeficiency Virus (SIV)-Infected Female Rhesus Macaques.

Title: Proteomic Analysis of Chronic Binge Alcohol-Induced Hippocampal and Anterior Cingulate Cortex Neuroadaptations in Simian Immunodeficiency Virus (SIV)-Infected Female Rhesus Macaques.
Authors: Fitzpatrick-Schmidt T; Department of Physiology, LSU Health-New Orleans, 1901 Perdido St. MEB 7205, New Orleans, LA, 70112, USA.; Alcohol & Drug Abuse Center of Excellence, LSU Health-New Orleans, New Orleans, USA.; Comprehensive Alcohol-HIV/AIDS Research Center, LSU Health-New Orleans, New Orleans, USA.; Mansouri A; Proteomics Core, LSU Health-New Orleans, New Orleans, USA.; Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, LSU Health-New Orleans, New Orleans, USA.; Adamec J; Proteomics Core, LSU Health-New Orleans, New Orleans, USA.; Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, LSU Health-New Orleans, New Orleans, USA.; Klein J; Proteomics Core, LSU Health-New Orleans, New Orleans, USA.; Coleman L; Comprehensive Alcohol-HIV/AIDS Research Center, LSU Health-New Orleans, New Orleans, USA.; Edwards KN; Department of Physiology, LSU Health-New Orleans, 1901 Perdido St. MEB 7205, New Orleans, LA, 70112, USA.; Simon L; Department of Physiology, LSU Health-New Orleans, 1901 Perdido St. MEB 7205, New Orleans, LA, 70112, USA.; Alcohol & Drug Abuse Center of Excellence, LSU Health-New Orleans, New Orleans, USA.; Comprehensive Alcohol-HIV/AIDS Research Center, LSU Health-New Orleans, New Orleans, USA.; Molina PE; Department of Physiology, LSU Health-New Orleans, 1901 Perdido St. MEB 7205, New Orleans, LA, 70112, USA.; Alcohol & Drug Abuse Center of Excellence, LSU Health-New Orleans, New Orleans, USA.; Comprehensive Alcohol-HIV/AIDS Research Center, LSU Health-New Orleans, New Orleans, USA.; Salling MC; Alcohol & Drug Abuse Center of Excellence, LSU Health-New Orleans, New Orleans, USA.; Comprehensive Alcohol-HIV/AIDS Research Center, LSU Health-New Orleans, New Orleans, USA.; Department of Cell Biology and Anatomy, LSU Health-New Orleans, New Orleans, LA, USA.; Edwards S; Department of Physiology, LSU Health-New Orleans, 1901 Perdido St. MEB 7205, New Orleans, LA, 70112, USA. sedwa5@lsuhsc.edu.; Alcohol & Drug Abuse Center of Excellence, LSU Health-New Orleans, New Orleans, USA. sedwa5@lsuhsc.edu.; Neuroscience Center of Excellence, LSU Health-New Orleans, New Orleans, USA. sedwa5@lsuhsc.edu.; Comprehensive Alcohol-HIV/AIDS Research Center, LSU Health-New Orleans, New Orleans, USA. sedwa5@lsuhsc.edu.
Source: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2025 Feb 10; Vol. 20 (1), pp. 16. Date of Electronic Publication: 2025 Feb 10.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Springer Science + Business Media Country of Publication: United States NLM ID: 101256586 Publication Model: Electronic Cited Medium: Internet ISSN: 1557-1904 (Electronic) Linking ISSN: 15571890 NLM ISO Abbreviation: J Neuroimmune Pharmacol Subsets: MEDLINE
Imprint Name(s): Original Publication: New York, NY : Springer Science + Business Media, c2006-
MeSH Terms: Simian Acquired Immunodeficiency Syndrome*/metabolism ; Hippocampus*/metabolism ; Hippocampus*/drug effects ; Proteomics*/methods ; Gyrus Cinguli*/metabolism ; Gyrus Cinguli*/drug effects ; Binge Drinking*/metabolism; Animals ; Female ; Macaca mulatta ; Simian Immunodeficiency Virus ; Ethanol
Abstract: Human immunodeficiency virus (HIV) infection produces neurological comorbidities including HIV-associated neurocognitive disorder (HAND) and chronic pain. HIV also increases the risk of developing an alcohol use disorder (AUD). With the rising prevalence of AUD in women and people with HIV (PWH), understanding the neurobiological impact of alcohol in these populations is important. We examined proteomic alterations in the hippocampus and anterior cingulate cortex (ACC), brain regions critical for cognition and affective pain, in a female rhesus macaque model of chronic binge alcohol administration and SIV infection. Adult female rhesus macaques received either chronic binge alcohol (CBA, 13-14 g/kg/week of alcohol) or water (VEH) via gastric catheter. All animals were inoculated with simian immunodeficiency virus (SIVmac251) and treated with antiretroviral therapy (ART). Brain samples were processed for proteomic analysis, and quantitative discovery-based proteomics identified differentially expressed proteins in both brain regions comparing CBA treatment to VEH. Ingenuity Pathway Analysis (IPA) was also used to predict pathway activation. CBA significantly altered 147 proteins in the hippocampus and 176 proteins in the ACC. IPA revealed alterations in 39 canonical pathways in the hippocampus and 62 canonical pathways in the ACC. Fourteen common canonical pathways were enriched in both regions, including synaptogenesis and protein kinase A (PKA) signaling. These discoveries expand our understanding of how alcohol alters proteins of critical signaling pathways in vulnerable brain regions in the context of SIV/HIV infection and may lead to the development of new pharmacological treatment avenues for neurological dysfunction in women with HIV who use alcohol.; (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Competing Interests: Declarations. None to report. Competing Interests: The authors declare no competing interests.
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Grant Information: P60 AA009803 United States AA NIAAA NIH HHS; F30AA030941 United States NH NIH HHS; F30 AA030941 United States AA NIAAA NIH HHS; T35 AA021097 United States AA NIAAA NIH HHS; P60AA009803 United States NH NIH HHS; R01AA025996 United States NH NIH HHS; T32 AA007577 United States AA NIAAA NIH HHS; R01 AA025996 United States AA NIAAA NIH HHS
Contributed Indexing: Keywords: Alcohol; Anterior cingulate cortex; Cognition; Hippocampus; Proteomics; Simian immunodeficiency virus
Substance Nomenclature: 3K9958V90M (Ethanol)
Entry Date(s): Date Created: 20250210 Date Completed: 20250507 Latest Revision: 20250520
Update Code: 20260130
PubMed Central ID: PMC12085871
DOI: 10.1007/s11481-025-10179-5
PMID: 39930298
Database: MEDLINE

Journal Article