Cell-type-specific whole-genome landscape of ΔFOSB binding in nucleus accumbens after chronic cocaine exposure
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ABSTRACT:
PROVIDER: PRJNA811531 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18183700_1.fastq.gz | Fastqsanger.gz | |||
| SRR18183700_2.fastq.gz | Fastqsanger.gz | |||
| SRR18183800_1.fastq.gz | Fastqsanger.gz | |||
| SRR18183800_2.fastq.gz | Fastqsanger.gz | |||
| SRR18183900_1.fastq.gz | Fastqsanger.gz |
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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.
2019-04-09 | GSE129462 | GEO
Project description:Cocaine use disorder (CUD) is a chronic neuropsychiatric condition characterized by a compulsion to use cocaine, resulting from enduring cellular and molecular adaptations. Among substance use disorders (SUDs), CUD is notable for its rising prevalence and the lack of approved pharmacotherapies. The nucleus accumbens (NAc), integral to the brain's reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook an in-depth proteomic analysis of the NAc in a mouse model that spans membrane, cytosolic, nuclear, and chromatin compartments. Our study unveils immediate and sustained proteomic modifications post-cocaine exposure and during prolonged withdrawal. We identify congruent protein regulatory patterns during initial cocaine exposure and re-exposure post-withdrawal, contrasted against distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicate adaptive and long-lasting molecular responses prompted by cocaine withdrawal. Additionally, we describe protein translocation events between soluble-nuclear and chromatin-bound compartments, providing novel insight into intracellular protein dynamics post-cocaine exposure. Together, our findings illuminate the intricate proteomic landscape altered in the NAc by cocaine and provide a comprehensive dataset for future research toward potential therapeutics.
2025-05-06 | PXD050162 | Pride
Project description:Background The ability of neurons to respond to external stimuli involves adaptations of gene expression. Induction of the transcription factor, ΔFOSB, in the nucleus accumbens (NAc), a key brain reward region, is important for the development of drug addiction. However, a comprehensive map of ΔFOSB’s gene targets has not yet been generated. Methods We use CUT&RUN to map the genome-wide changes in ΔFOSB binding in the two main types of NAc neurons—D1 or D2 medium spiny neurons (MSNs)—after chronic cocaine exposure. To annotate genomic regions of ΔFOSB binding sites, we also examined the distributions of several histone modifications. Resulting datasets were leveraged for multiple bioinformatic analyses. Results The majority of ΔFOSB peaks occur outside of promoter regions, including intergenic regions, and are surrounded by epigenetic marks indicative of active enhancers. BRG1, the core subunit of the SWI/SNF chromatin remodeling complex, overlaps with ΔFOSB peaks, consistent with earlier studies of ΔFOSB’s interacting proteins. Chronic cocaine induces broad changes in ΔFOSB binding in both D1 and D2 NAc MSNs of male and female mice. In addition, in silico analyses predict that ΔFOSB cooperatively regulates gene expression with homeobox and T-box transcription factors. Conclusions These novel findings uncover key elements of ΔFOSB’s molecular mechanisms in transcriptional regulation at baseline and in response to chronic cocaine exposure. Further characterization of ΔFOSB’s collaborative transcriptional and chromatin partners specifically in D1 and in D2 MSNs will reveal a broader picture of the function of ΔFOSB and the molecular basis of drug addiction.
2022-07-08 | GSE197668 | GEO
Project description:Total RNA-sequencing of FACs isolated nucleus accumbens somatostatin interneuron nuclei Somatostatin interneuron loss in multiple cortical brain regions has been observed postmortem in humans with several neuropsychiatric disorders and their loss is proposed to underlie some common pathological changes in circuit function across numerous syndromes. However, somatostatin interneurons in the nucleus accumbens (NAc), a key brain reward region, remain poorly understood due to the fact that these cells account for <1% of NAc neurons. Here, we used Flouresence activated cell sorting to isolate nuclei of somatostatin-expressing interneurons in the Nucleus Accumbens from individual SST-TLG498 reporter mice that express membrane bound EGFP-F specifically in somatostatin-expressing neurons. We then performed cell-type specific Total RNA-sequencing to characterize the entire transcriptome of NAc somatostatin interneurons after repeated exposure (7 days) to either saline or cocaine. We identified a wide variety of coding and non-coding transcripts that were expressed at high levels and were differentially expressed between saline and cocaine treated mice. Repeated cocaine administration induces transcriptome-wide changes in gene expression within NAc somatostatin interneurons, with particular regulation of transcripts related to neural plasticity. Our results identify alterations in NAc induced by cocaine in a sparse population of somatostatin interneurons, and illustrate the value of studying brain diseases using cell type-specific whole transcriptome RNA-sequencing to identify novel neurpathophysiology.
2018-07-03 | GSE116484 | GEO
Project description:Genetic association studies, pharmacological investigations and analysis of mice-lacking individual genes have made it clear that Cocaine administration and Withdrawal have a profound impact on multiple neurotransmitter systems. The GABAergic medium spiny neurons of the nucleus accumbens (NAc) exhibit changes in the expression of genes encoding receptors for glutamate and in the signaling pathways triggered by dopamine binding to G-protein-coupled dopamine receptors. Deep sequence analysis provides a sensitive, quantitative and global analysis of the effects of Cocaine on the NAc transcriptome. RNA prepared from the NAc of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal, was used for high-throughput sequence analysis. Changes were validated by quantitative polymerase chain reaction or Western blot. On the basis of pathway analysis, a preponderance of the genes affected by Cocaine and Withdrawal was involved in the cadherin, heterotrimeric G-protein and Wnt signaling pathways. Distinct subsets of cadherins and protocadherins exhibited a sustained increase or decrease in expression. Sustained down-regulation of several heterotrimeric G-protein β- and γ-subunits was observed. In addition to altered expression of receptors for small molecule neurotransmitters, neuropeptides and endocannabinoids, changes in the expression of plasma membrane transporters and vesicular neurotransmitter transporters were also observed. The effects of chronic Cocaine and Withdrawal on the expression of genes essential to cholinergic, glutamatergic, GABAergic, peptidergic and endocannabinoid signaling are as profound as their effects on dopaminergic transmission. Simultaneous targeting of multiple Withdrawal-specific changes in gene expression may facilitate development of new therapeutic approaches that are better able to prevent relapse. High-throughput sequence analysis of RNA prepared from the nucleus accumbens of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal. Nucleus accumbens libraries were sequenced in nine lanes (three technical replicates per sample) on an Illumina GAIIx using a 37-cycle paired-end sequencing protocol. Replicates were analyzed for intra-sample disparity and read data from all three lanes were then merged into one composite data file per sample; intra-sample coefficient of determination, R2 ≥ 0.98. The composite file was used for subsequent analyses.
2013-01-10 | E-GEOD-43410 | biostudies-arrayexpress
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine, were subjected to 30 withdrawal days, were treated with aCSF, RG108 or SAM and were subjected to extinction tests. The groups consist of: 1. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with aCSF and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (aCSF) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with RG108 and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (RG108) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with SAM and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (SAM)
2015-02-27 | E-GEOD-66347 | biostudies-arrayexpress
Project description:Long read sequencing of mouse nucleus accumbens in chronic cocaine treatment
| PRJNA531432 | ENA
Project description:Prior research demonstrated that environmental enrichment creates individual differences in behavior leading to a protective addiction phenotype in rats. Understanding the mechanisms underlying this phenotype will guide selection of targets for much-needed novel pharmacotherapeutics. The current study investigates basal differences in proteome expression in the nucleus accumbens of enriched and isolated rats and the proteomic response to cocaine self-administration using a liquid chromatography mass spectrometry (LCMS) technique to quantify 1917 proteins. Results of complementary Ingenuity Pathways Analyses (IPA) and gene set enrichment analyses (GSEA) demonstrate that cocaine increases vesicular transporters for dopamine and glutamate, as well as increasing proteins in the RhoA pathway. Further, cocaine regulates proteins related to ERK, CREB and AKT signaling. Environmental enrichment altered expression of a large number of proteins with diverse functions, including mood disorders, energy production, ubiquitination, splicing, transport, kinases and neurodegenerative diseases. Most of the biological functions and pathways listed above were also identified in the Cocaine X Enrichment interaction analysis, providing clear evidence that enriched and isolated rats respond quite differently to cocaine exposure. The overall impression of the current results is that enriched saline-administering rats have a unique proteomic complement compared to enriched cocaine-administering rats as well as saline and cocaine-taking isolated rats. These results identify possible mechanisms of the protective phenotype and provide fertile soil for developing novel pharmacotherapeutics.
2014-07-22 | PXD000990 | Pride
Project description:Gene expression profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
2015-02-27 | GSE66349 | GEO
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
2015-02-27 | GSE66348 | GEO