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Epigenetic Moderators of Naltrexone Efficacy for Alcohol Use Disorder

ABSTRACT: Epigenetic Moderators of Naltrexone Efficacy for Alcohol Use Disorder

PROVIDER: PRJNA729135 | 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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Project description:Excessive alcohol consumption is a leading cause of preventable death worldwide. Neurobiological mechanisms associated with alcohol use disorder (AUD) remain insufficiently understood. Here, we provide RNA-sequencing data generated in nucleus accumbent and dorsolateral prefrontal cortex, from 114 deceased individuals: 58 AUD cases, 56 non-AUD controls. DNA methylation data on many of these same individuals is available (see GEO accession number GSE252501).

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2023-10-24 | PXD040884 | Pride

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

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Presynaptic proteins in the orbitofrontal cortex predict Alcohol Use Disorder

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.

2023-10-09 | PXD041727 | Pride

Epigenetic profiling of Fetal Alcohol Spectrum Disorder (FASD)

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

Project description:Purpose: The goal of this study to examine mRNA transcriptomic changes in reward-related brain regions of subjects with alcohol use disorder. Methods: Total RNAs were extracted from postmortem putamen of 12 AUD and 12 control subjects. rRNA depletion RNA sequencing was performed and the sequence reads were processed using the bulk RNA-seq processing pipeline Pipeliner workflow (Federico et al. Front Genet 2019; 10, 614). AUD-associated mRNA transcriptomic changes were analyzed by the Limma-Voom method. Results: Differentially expressed mRNAs (absolute FC>2.0 & P<0.05) were identified in postmortem putamen of subjects with alcohol use disorder (AUD). Chronic alcohol consumption may alter mRNA transcriptome profiles in reward-related brain regions, resulting in alcohol-induced neuroadaptations.

2021-10-13 | GSE182440 | GEO

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2021-10-13 | GSE181981 | GEO

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