Adult nucleus accumbens single-nucleus RNA-seq dataset for "Distinct subpopulations of D1 medium spiny neurons exhibit unique transcriptional responsiveness to cocaine"
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ABSTRACT:
PROVIDER: PRJNA922049 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23021848.fastq.gz | Fastqsanger.gz | |||
| SRR23021849.fastq.gz | Fastqsanger.gz | |||
| SRR23021850.fastq.gz | Fastqsanger.gz | |||
| SRR23021851.fastq.gz | Fastqsanger.gz | |||
| SRR23021852.fastq.gz | Fastqsanger.gz |
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Project description:This dataset contains single-nucleus RNA sequencing results from adult rat brain (nucleus accumbens) and serves as the basis for characterization of transcriptional response to repeated cocaine injections (20mg/kg, intraperitoneal injection). The goal of this experiment was to define the transcriptional response to repeated cocaine across distinct cell types in the nucleus accumbens. Single-cell sequencing was carried out with FACS-sorted nuclei isolated from these experiments using the 10X Genomics Chromium single cell sequencing platform.
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Project description:Substance use disorders (SUDs) induce widespread molecular dysregulation in nucleus accumbens (NAc), a brain region pivotal for coordinating motivation and reward, which is linked to neural and behavioral disturbances promoting addiction. Despite the overlapping symptomatology of SUDs, different drug classes exert partly unique influences on neural circuits, cell types, physiology, and gene expression. To better understand common and divergent molecular mechanisms governing SUD pathology, we characterized the cell-type-specific restructuring of the NAc transcriptional landscape after psychostimulant or opioid exposure. We combined fluorescence-activated nuclei sorting and RNA sequencing to profile NAc D1 and D2 medium spiny neurons (MSNs) across cocaine exposure paradigms, including initial exposure, prolonged withdrawal after repeated exposure, and re-exposure post-withdrawal. Our analyses reveal that D1 MSNs display many convergent transcriptional responses across the two drugs, whereas D2 MSNs manifest highly divergent responses, with morphine causing far more adaptations in this cell type.
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Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in medium spiny neurons in the accumbens nucleus of adult Drd2-EGFP/Rpl10a (CP101) mice that were administered either saline or cocaine under long access conditions
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Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in medium spiny neurons in the accumbens nucleus of adult Drd1-EGFP/Rpl10a (CP73) mice that were administered either saline or cocaine under long-access conditions
2019-12-16 | GSE141667 | 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:Shared and divergent transcriptomic regulation in nucleus accumbens D1 and D2 medium spiny neurons by cocaine
| PRJNA1138820 | ENA
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:Despite addiction being one of the most prevalent and debilitating disorders worldwide, effective treatments are lacking. Repeated cocaine exposure induces maladaptive transcriptional regulation within the brainâ??s reward circuitry, such as the nucleus accumbens (NAc), and epigenetic mechanisms, such as histone acetylation or methylation on Lys (K) residues, have been linked to these lasting actions of cocaine. However, in contrast to K methylation, the functional role of histone Arg (R) methylation remains unexplored in addiction models and poorly understood in brain in general. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, as well as in the NAc of cocaine-addicted humans. PRMT6 downregulation occurs selectively in NAc medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) and serves to protect against cocaine-induced addictive-like behavioral abnormalities. Using ChIP-seq, we demonstrate that reduced H3R2me2a binding at gene targets in NAc after repeated cocaine is strongly correlated with increased binding of H3K4me3, and identify Src kinase signaling inhibitor 1 (Srcin1 or p140Cap) as a key gene for these chromatin modifications. Cocaine induction of Srcin1 in NAc, which is associated with reduced Src signaling, decreases cocaine reward, the motivation to self administer cocaine, and cocaine-induced changes in NAc MSN dendritic spines. These results suggest that this suppression of Src signaling in NAc D2-MSNs, via PRMT6 and H3R2me2a downregulation, functions as a homeostatic brake to restrain cocaine action, and provide novel candidates for the development of new treatments for cocaine addiction. H3R2me2A ChIP-seq of mouse. Cocaine vs Saline, 3 biological replicates.
2016-08-08 | E-GEOD-85310 | biostudies-arrayexpress
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.
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