Multi-omics analysis of cocaine use disorder in postmortem brain tissue of the ventral striatum [Proteomics data to study EGAS50000000623]
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PROVIDER: EGAS00001007945 | EGA |
REPOSITORIES: EGA
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Project description:<p>This project characterizes DNA methylation and gene expression changes that occur in the human brain, specifically in neurons from the rostral striatum. Major advances from NIDA funded initiatives for noninvasive neuroimaging studies have made it possible to study neuroanatomical, neurochemical and functional changes in the human brain that contribute to the vulnerability to abuse drugs, together with the neurotoxic consequences of years of drug misuse. Animal models have been developed to explain the fundamental behavioral and biological mechanisms of addiction, including reward, tolerance and dependence. From these studies, we learned that cocaine abuse not only alters the epigenetic status of genes, but also induces particular epigenetic modifications depending on the frequency of the drug's administration. Certain genes are switched on by infrequent (short-term exposure) administration, while others are switched on only after chronic administration (addiction/dependence). Animal studies have also suggested that cocaine-seeking habits modeling chronic cocaine addiction in humans depend upon dopamine-dependent serial connectivity linking the ventral (nucleus accumbens) with the dorsal striatum (caudate nucleus). The primary goal of this study is to identify DNA methylation and gene expression changes that occur in the transition from recreational cocaine use to cocaine addiction. High throughput sequencing studies were designed to investigate unique postmortem human brain specimens from individuals that met criteria for cocaine dependence, as compared to unaffected age-matched controls.</p> <p>Brain biospecimens were available from the University of Miami Brain Endowment BankTM, from a collection of phenotypically well-characterized postmortem tissues sampled from chronic cocaine abusers that came to autopsy. This biobank of postmortem brain specimens and annotated genomic data serve as a research resource to support NIDA's scientific mission.</p>
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Project description:Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a significant public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from postmortem brains of subjects with CUD and matched control subjects. Weighted gene co-expression analyses identified CUD-specific gene networks enriched in ionotropic receptors and associated with lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.
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Project description:Single nuclei RNA sequencing (snRNA-seq) dataset characterizing astrocytes and oligodendrocytes isolated from human postmortem APOE e2/3 Alzheimer's disease (AD) and aged-matched non-symptomatic (NS) brains.
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Project description:To better understand the transcriptome of Nucleus Accumbens (NAc) – a key brain reward region – under chronic cocaine treatment, we perform the first Iso-Seq analysis on its mRNAs to determine the full-length transcripts without assembly.
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Project description:Multidimensional Top-Down Proteomics of Brain Region-Specific Mouse Brain Proteoforms Responsive to Cocaine and Estradiol
2018-11-02 | MSV000083093 | MassIVE
Project description:Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on the brain, and recent work has demonstrated the involvement of chromatin modifications in these alterations. However, all such studies to date have been restricted by their reliance on microarray technologies which have intrinsic limitations. Here, we used advanced sequencing methods, RNA-seq and ChIP-seq, to obtain an unprecedented view of cocaine-induced changes in gene expression and associated adaptations in numerous modes of chromatin regulation in the nucleus accumbens, a key brain reward region. We identify unique combinations of chromatin changes, or signatures, that accompany cocaineM-bM-^@M-^Ys regulation of gene expression, including the dramatic involvement of pre-mRNA alternative splicing in cocaine action. Together, this delineation of the cocaine-induced epigenome in the nucleus accumbens reveals several novel modes of drug regulation, thereby providing new insight into the biological basis of cocaine addiction. More broadly, the combinatorial chromatin and transcriptional approaches that we describe serve as an important resource for the field, as they can be applied to other systems to reveal novel transcriptional and epigenetic mechanisms of neuronal regulation. Total RNA was isolated from mouse nucleus accumbens 24 hr after 7 day daily cocaine or saline control ip injection for mRNA sequencing by following illumina RNA seq kit protocol. Another batch of acute cocaine RNA-seq was performed using the same parameters except the treatment group was given 6 days of saline injection followed by 1 day of cocaine injection. The acute cocaine batch serves as control experiments.
2014-02-14 | E-GEOD-42805 | biostudies-arrayexpress
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.
2023-02-01 | GSE221515 | GEO
Project description:Analysis of cocaine use disorder (CUD) associated epigenome-wide DNA methylation (DNAm) alterations in human postmortem brain tissue of Brodmann Area 9. Tissue samples from N=21 CUD cases and N=21 individuals without CUD originating from the Douglas Bell Canada Brain Bank (DBCBB) were included. Epigenome-wide DNAm was investigated using the Illumina Infinium MethylationEPIC array.
| EGAD00010002396 | EGA
Project description:Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on the brain, and recent work has demonstrated the involvement of chromatin modifications in these alterations. However, all such studies to date have been restricted by their reliance on microarray technologies which have intrinsic limitations. Here, we used advanced sequencing methods, RNA-seq and ChIP-seq, to obtain an unprecedented view of cocaine-induced changes in gene expression and associated adaptations in numerous modes of chromatin regulation in the nucleus accumbens, a key brain reward region. We identify unique combinations of chromatin changes, or signatures, that accompany cocaine’s regulation of gene expression, including the dramatic involvement of pre-mRNA alternative splicing in cocaine action. Together, this delineation of the cocaine-induced epigenome in the nucleus accumbens reveals several novel modes of drug regulation, thereby providing new insight into the biological basis of cocaine addiction. More broadly, the combinatorial chromatin and transcriptional approaches that we describe serve as an important resource for the field, as they can be applied to other systems to reveal novel transcriptional and epigenetic mechanisms of neuronal regulation. ChIP-seq of 6 marks (H3K27me3, H3K36me3, H3K4me1, H3K4me3, H3K9me2, RNApolII) were done on mouse nucleus accumbens 24 hr after 7 day daily cocaine ip injection with saline as control. Three replicates for each condition.
2014-02-14 | E-GEOD-42810 | biostudies-arrayexpress