Effects of repeated alcohol abstinence on within-subject prefrontal cortical gene expression in rhesus macaques.

Autor: Hitzemann R; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States.; Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States.; Veterans Affairs Portland Health Care System, Portland, OR, United States., Gao L; Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States.; Bioinformatics and Biostatistics Core, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Fei SS; Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States.; Bioinformatics and Biostatistics Core, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Ray K; Bioinformatics and Biostatistics Core, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Vigh-Conrad KA; Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Phillips TJ; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States.; Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States.; Veterans Affairs Portland Health Care System, Portland, OR, United States., Searles R; Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States.; Integrated Genomics Laboratory, Oregon Health and Science University, Portland, OR, United States., Cervera-Juanes RP; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Khadka R; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Carlson TL; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Gonzales SW; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Newman N; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Grant KA; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States.; Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, United States.; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States.
Jazyk: angličtina
Zdroj: Advances in drug and alcohol research [Adv Drug Alcohol Res] 2024 Apr 26; Vol. 4, pp. 12528. Date of Electronic Publication: 2024 Apr 26 (Print Publication: 2024).
DOI: 10.3389/adar.2024.12528
Abstrakt: Male rhesus monkeys ( n = 24) had a biopsy of prefrontal cortical area 46 prior to chronic ethanol self-administration ( n = 17) or caloric control ( n = 7). Fourteen months of daily self-administration (water vs. 4% alcohol, 22 h access/day termed "open-access") was followed by two cycles of prolonged abstinence (5 weeks) each followed by 3 months of open-access alcohol and a final abstinence followed by necropsy. At necropsy, a biopsy of Area 46, contralateral to the original biopsy, was obtained. Gene expression data (RNA-Seq) were collected comparing biopsy/necropsy samples. Monkeys were categorized by drinking status during the final post-abstinent drinking phase as light (LD), binge (BD), heavy (HD) and very heavy (VHD drinkers). Comparing pre-ethanol to post-abstinent biopsies, four animals that converted from HD to VHD status had significant ontology enrichments in downregulated genes (necropsy minus biopsy n = 286) that included immune response (FDR < 9 × 10 -7 ) and plasma membrane changes (FDR < 1 × 10 -7 ). Genes in the immune response category included IL16 and 18 , CCR1 , B2M , TLR3 , 6 and 7 , SP2 and CX3CR1 . Upregulated genes ( N = 388) were particularly enriched in genes associated with the negative regulation of MAP kinase activity (FDR < 3 × 10 -5 ), including DUSP 1 , 4 , 5 , 6 and 18 , SPRY 2 , 3 , and 4 , SPRED2 , BMP4 and RGS2 . Overall, these data illustrate the power of the NHP model and the within-subject design of genomic changes due to alcohol and suggest new targets for treating severe escalated drinking following repeated alcohol abstinence attempts.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Hitzemann, Gao, Fei, Ray, Vigh-Conrad, Phillips, Searles, Cervera-Juanes, Khadka, Carlson, Gonzales, Newman and Grant.)
Databáze: MEDLINE
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