Project description:Analysis of methylomic alternations related with alcohol use disorders (AUD). The hypothesis is that chronic alcohol consumption might alter genome-wide DNA methylation patterns. The results suggest that differential DNA methylation might be invovled in neuradaptations to alcohol. Genomic DNA was extraced from postmortem prefrontal cortex tissues of 23 AUD cases and 23 matched controls. Both AUD cases and matched controls are assessed with DSM-IV
Project description:Analysis of transcriptiomic alternations related with alcohol use disorders (AUDs). The hypothesis is that chronic alcohol consumption might alter genome-wide gene expression patterns. The results suggest that differential gene expression in the prefrontal cortex is implicated in neuroadaptations to alcohol. Total RNAs were extracted from postmortem prefrontal cortex tissues from 23 AUD cases and 23 matched controls. Both AUD cases and matched controls were assessed with DSM-IV.
Project description:Analysis of methylomic alternations related with alcohol use disorders (AUD). The hypothesis is that chronic alcohol consumption might alter genome-wide DNA methylation patterns. The results suggest that differential DNA methylation might be invovled in neuradaptations to alcohol.
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.
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).
Project description:The present study utilized patient-derived “cell-line” model systems treated with anti-craving drugs that are used to treat alcohol use disorder (AUD) as “molecular probes” to help identify molecular mechanisms associated with craving and AUD treatment outcomes.
Project description:Alcohol use disorder (AUD) affects transcriptomic, epigenetic and proteomic expression in several organs including the brain. Multi-omic analyses of the brain from individuals with AUD to date lack a comprehensive analysis of protein alterations in the multiple brain regions that underlie neuroadaptations occurring in AUD. We performed quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of human post-mortem tissue from brain regions that play a key role in the development and maintenance of AUD: amygdala (AMG), hippocampus (HIPP), hypothalamus (HYP), nucleus accumbens (NAc), prefrontal cortex (PFC) and ventral tegmental area (VTA). Brain tissues analyzed were from individuals with AUD (n = 11) and matched controls (n = 16).
Project description:Alcohol use disorders (AUD) are one of the most common preventable mental health disorders and can result in pathology within the CNS, including the cerebellum. Cerebellar alcohol exposure during adulthood has been associated with disruptions in proper cerebellar function. However, the mechanisms regulating ethanol-induced cerebellar neuropathology are not well understood. High-throughput next generation sequencing was performed to compare control versus ethanol treated adult C57BL/6J mice in a chronic plus binge model of AUD. Mice were euthanized, cerebella were microdissected, RNA was isolated, and RNA-sequencing was performed. Down-stream transcriptomic analyses revealed significant changes in gene expression and global biological pathways in control versus ethanol treated mice that included pathogen-influenced signaling pathways and cellular immune response pathways. Microglial associated genes showed a decrease in homeostatic molecules and an increase in molecules associated with chronic neurodegenerative diseases, while astrocyte associated genes showed an increase in molecules associated with acute injury. Oligodendrocyte lineage cell genes showed a decrease in molecules associated with both early-stage progenitors as well as mature myelinating oligodendrocytes. These data provide new insight into the mechanisms by which ethanol induces cerebellar neuropathology and alterations to the immune response in AUD.
Project description:Analysis of transcriptiomic alternations related with alcohol use disorders (AUDs). The hypothesis is that chronic alcohol consumption might alter genome-wide gene expression patterns. The results suggest that differential gene expression in the prefrontal cortex is implicated in neuroadaptations to alcohol.