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A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response

ABSTRACT: A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response

PROVIDER: PRJNA565944 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10131210_1.fastq.gz	Fastqsanger.gz
	SRR10131210_2.fastq.gz	Fastqsanger.gz
	SRR10131211_1.fastq.gz	Fastqsanger.gz
	SRR10131211_2.fastq.gz	Fastqsanger.gz
	SRR10131212_1.fastq.gz	Fastqsanger.gz

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A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response

Project description:The goal of this experiment was to determine how dopamine receptor activation in medium spiny neurons alters rapid transcriptional programs. To identify genes altered by dopamine, we used a rat primary striatal neuronal culture system in which striatal neurons were removed from the rat brain at embryonic day 18, cultured for 11 days in vitro using standard neuronal conditions, and treated neurons with either vehicle (neurobasal media) or dopamine (at a concentration of 1µM) for 1hr. This dataset contains PolyA+ RNA-seq results from this experiment, in which we identified 100 upregulated genes and 3 downregulated genes after dopamine stimulation using DESeq2 pipelines.

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Dopaplex RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

Project description:Dopaplex RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

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Adult nucleus accumbens single-nucleus RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

Project description:Adult nucleus accumbens single-nucleus RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

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Striatal cultured neurons single-nucleus RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

Project description:Striatal cultured neurons single-nucleus RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

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Dopaplex RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

Project description:This dataset contains whole-genome RNA sequencing results from rat embryonic striatal neuronal cultures and serves as the basis for characterization of multiplexed CRISPR/dCas9 gene activation of 16 genes induced by dopamine receptor activation. The goal of this experiment was to define the transcriptional response to multiplexed CRISPR-based upregulation of 16 dopamine-induced genes (Tent5b, Junb, Prox1, Nr4a2, Nptx1, Gsx1, Gadd45g, Btg2, Fosb, Nr4a1, Egr4, Fos, Sstr2, Gadd45b, Egr3, & Egr2), together termed "Dopaplex", as compared to a LacZ control sgRNA.

2020-06-24 | GSE137658 | GEO

Cocaine-craving drives repressive epigenetic differential gene expression in ventral tegmental area dopamine neurons

Project description:Dopamine (DA) signaling plays an essential role in reward valence attribution and in encoding the reinforcing properties of natural and artificial rewards. The adaptive responses from midbrain dopamine neurons to artificial rewards such as drugs of abuse are therefore important for understanding the development of substance use disorders. Drug-induced changes in gene expression are one such adaptation that can determine the activity of dopamine signaling in projection regions of the brain reward system. One of the major challenges to obtaining this understanding is the inherent cellular heterogeneity in the brain, where each neuron population can be defined by a distinct transcriptional profile. To bridge this gap, we have adapted a virus-based method for labeling and capture of dopamine nuclei, coupled with nuclear RNA-sequencing and bioinformatics analyses, to study the transcriptional adaptations, specifically, of dopamine neurons in the ventral tegmental area (VTA) during cocaine taking and cocaine craving, using a mouse model of cocaine intravenous self-administration (IVSA). Our results show significant changes in gene expression across non-drug operant training, cocaine taking, and cocaine craving, highlighted by an enrichment in expression of repressive epigenetic modifying enzymes during cocaine craving. Immunohistochemical validation further revealed an increase of H3K9me3 deposition in DA neurons during cocaine craving. These results demonstrate that cocaine-induced transcriptional adaptations in dopamine neurons vary by phase of self-administration and suggest that such an approach may be useful in identifying relevant phase-specific molecular targets to alter the behavioral course of substance use disorders.

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Striatal cultured neurons single-nucleus RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

Project description:This dataset contains single-nucleus RNA sequencing results from rat embryonic striatal neuronal cultures and serves as the basis for characterization of transcriptional response to dopamine (50µM), the Drd1 agonist SKF-38393 (1µM), and potassium chloride (25mM). The goal of this experiment was to define the transcriptional response to each of these stimulations across distinct cell types in cultured neurons. Single-cell sequencing was carried out on FACS-sorted nuclei isolated from these experiments using the 10X Genomics Chromium single cell sequencing platform.

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Adult nucleus accumbens single-nucleus RNA-seq dataset for "A dopamine-induced coordinated gene expression program regulates neuronal function and cocaine response"

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 cocaine (20mg/kg, intraperitoneal injection). The goal of this experiment was to define the transcriptional response to cocaine across distinct cell types in the nucleus accumbens. Single-cell sequencing was carried out on FACS-sorted nuclei isolated from these experiments using the 10X Genomics Chromium single cell sequencing platform.

2020-06-24 | GSE137763 | GEO

A molecular profile of chronic cocaine abuse includes differential expression of genes regulating transcription, chromatin and dopamine cell phenotype

Project description:Midbrain dopamine (DA)-synthesizing neurons play a key role in the addiction process, providing a compelling rationale for determining drug-induced molecular changes arising in these cells. This microarray-based study determined the profiles of midbrain gene expression in chronic cocaine abusers (n = 10) and well-matched drug-free control subjects (n = 10). Array-related procedures were performed in triplicate for each subject. Data analysis revealed that 98 array probes (corresponding to 91 genes) exhibited robust, statistically significant expression differences between chronic cocaine abusers and matched control subjects (p ? 0.05, FDR = 5%; with ? 1.4 fold-change cut-off applied). Changes in transcript abundance identified by microarray were validated by qPCR analysis in every instance examined (n = 11), regardless of the direction or magnitude of change, supporting the validity of the larger dataset of genes differentially expressed in cocaine abusers. Many of the genes exhibiting robust differential expression were associated with the regulation of transcription, chromatin function, or dopamine cell phenotype. For approximately one-half of these genes, transcript abundance was significantly predictive for subject assignment to the cocaine-abusing versus control cohort. The findings suggest that there is a molecular signature associated with core pathophysiological changes in the DA neurons of chronic cocaine abusers that can be exploited for the development of potential biomarkers and novel therapeutic targets for addiction. Human post-mortem midbrain gene expression derived from cocaine-related deaths are compared to midbrain gene expression of non-cocaine related deaths. Each subject was was arrayed in triplicates.

2014-04-01 | E-GEOD-54839 | biostudies-arrayexpress

Reactive Oxygen Species Mediate Transcriptional Responses to Dopamine and Cocaine in Human Cerebral Organoids [Rudibaugh2023]

Project description:Dopamine signaling in the adult ventral forebrain regulates behavior, stress response, and memory formation and in neurodevelopment regulates neural differentiation and cell migration. Excessive dopamine levels including due to cocaine use both in utero and in adults could lead to long-term adverse consequences. The mechanisms underlying both homeostatic and pathological changes remain unclear, partly due to the diverse cellular responses elicited by dopamine and the reliance on animal models that exhibit species-specific differences in dopamine signaling. To address these limitations, 3-D cerebral organoids have emerged as human-derived models, recapitulating salient features of human cell signaling and neurodevelopment. Organoids have demonstrated responsiveness to external stimuli, including substances of abuse, making them valuable investigative models. In this study we utilize the Xiang-Tanaka ventral forebrain organoid model and characterize their response to acute and chronic dopamine or cocaine exposure. The findings revealed a robust immune response, novel response pathways, and a potential critical role for reactive oxygen species (ROS) in the developing ventral forebrain. These results highlight the potential of cerebral organoids as in vitro human models for studying complex biological processes in the brain.

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