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Epigenetic Moderators of Naltrexone Efficacy for Alcohol Use Disorder

ABSTRACT: Epigenetic Moderators of Naltrexone Efficacy for Alcohol Use Disorder

PROVIDER: PRJNA729134 | ENA |

REPOSITORIES: ENA

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Epigenetic Moderators of Naltrexone Efficacy for Alcohol Use Disorder

Project description:Epigenetic Moderators of Naltrexone Efficacy for Alcohol Use Disorder

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2023-10-24 | PXD040884 | Pride

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Project description:Alcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences, which are driven by dysfunction of cortical areas, such as the orbitofrontal cortex (OFC), that normally balances decisions related to reward and risk. In this study, proteomics and machine learning analysis of post-mortem OFC brain samples collected from individuals with AUD revealed dysregulation of presynaptic (e.g., AP2A1) and mitochondrial proteins that predicted the occurrence and severity of AUD. Alcohol-sensitive OFC proteins also mapped to abnormal social behaviors and interactions. Validation using reverse genetics, we found that prefrontal Ap2a1 regulates alcohol drinking in genetically diverse mouse strains. Furthermore, we demonstrated sexual dimorphism in human OFC proteins that regulate extracellular matrix structure and signaling. Together, these findings highlight the impact of excessive alcohol consumption on the human OFC proteome and identify important cross-species cortical mechanisms underlying AUD.

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Acamprosate, Craving and Alcohol Use Disorder: the Role of Inflammation

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Profiling of mRNA transcriptomic changes using RNA-seq in postmortem putamen of subjects with alcohol use disorder

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2021-10-13 | GSE182440 | GEO

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