Project description:Gene expression profile at single cell level of striatal cells from the caudate nucleus and putamen in postmortem human brains of unaffected individuals or those with opioid use disorder.
Project description:7 male OUD patients and 7 male health controls with demographic and clinical data matched were enrolled in this study. rRNA removed library and small RNA library were constructed using peripheral blood RNA. RNA-seq was used to investigate the peripheral transcriptomic changes between the two groups.
Project description:7 male OUD patients and 7 male health controls with demographic and clinical data matched were enrolled in this study. rRNA removed library and small RNA library were constructed using peripheral blood RNA. RNA-seq was used to investigate the peripheral transcriptomic changes between the two groups.
Project description:Differential expression analysis of human central Amygdala samples with a story of opioid use disorder (OUD) vs. unaffected control central Amygdala samples
Project description:Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC
Project description:Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD=12; non-OUD=26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.
Project description:This dataset includes samples in the UTHealth Brain Collection (UTHBC) from Grimm et al 2022 "MicroRNA-mRNA networks are dysregulated in opioid use disorder postmortem brain: further evidence for opioid-induced neurovascular alterations ", doi: 10.3389/fpsyt.2022.1025346. To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function. Building on the growing appreciation that miRNAs can cross the blood-brain barrier, we carried out miRNA profiling in same-subject postmortem samples from BA9 and blood tissues. miRNA-mRNA network analysis showed that even though miRNAs identified in BA9 and blood were fairly distinct, their target genes and corresponding enriched pathways overlapped strongly. Among the dominant enriched biological processes were tissue development and morphogenesis, and MAPK signaling pathways. These findings point to robust, redundant, and systemic opioid-induced miRNA dysregulation with potential functional impact on transcriptomic changes. Further, using correlation network analysis we identified cell-type specific miRNA targets, specifically in astrocytes, neurons, and endothelial cells, associated with OUD transcriptomic dysregulation. Finally, leveraging a collection of control brain transcriptomes from the Genotype-Tissue Expression (GTEx) project, we identified correlation of OUD miRNA targets with TGF beta, hypoxia, angiogenesis, coagulation, immune system and inflammatory pathways. These findings support previous reports of neurovascular and immune system alterations as a consequence of opioid abuse and shed new light on miRNA network regulators of cellular response to opioid drugs.