Effect of Chronic Ethanol Consumption in Rhesus Macaques on the Nucleus Accumbens Core Transcriptome
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ABSTRACT:
PROVIDER: PRJNA604902 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11024040_1.fastq.gz | Fastqsanger.gz | |||
| SRR11024040_2.fastq.gz | Fastqsanger.gz | |||
| SRR11024041_1.fastq.gz | Fastqsanger.gz | |||
| SRR11024041_2.fastq.gz | Fastqsanger.gz | |||
| SRR11024042_1.fastq.gz | Fastqsanger.gz |
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Project description:The current study was undertaken to expand on observations that transcriptome changes identified in the NAcc of Rhesus macaques underlies excessive ethanol consumption. Genome-wide RNA-Seq was used to examine the NAcc transcriptome in control, low/binge drinking and heavy/very heavy drinking animals. One key goal of the study was to determine if, as predicted and suggested by the epigenetic studies, excessive chronic ethanol consumption involves genes enriched in annotations associated with synaptic plasticity and specifically glutamate and GABA signaling plasticity.
2020-02-06 | GSE144783 | GEO
Project description:The study investigated ethanol-induced alterations in the transcriptome of adult male Wistar rats. The study was divided into two parts. Part 1: 10 animals were single housed during 8 weeks and exposed to 6% ethanol solution and water simultaneously or just water (24 hours/day, 7 days/week). Fluid intake and body weight were recorded twice weekly during 8 weeks. Animals were sacrificed immediately after the last consumption measurement and the nucleus accumbens were dissected and snap frozen until further processing. Part 2: 12 rats were single housed and exposed to continuous access to ethanol and water (24 hours/day, 7 days/week). After 4 weeks, animals were divided into 2 groups, equally balanced based on previous ethanol intake, and were given additional ethanol or water through a gavage tube daily during 3 weeks. This was followed by an additional 2 weeks of continuous ethanol access and then animals were immediately sacrificed and the nucleus accumbens were dissected and snap frozen until further processing. Next, the RNA was extracted from the cells using Qiagen RNeasy Lipid tissue mini kit and the RNA concentration and quality was measured using a BioAnalyzer. RNAseq was performed using standard Illumina protocols in collaboration with SciLifeLab, Stockholm, Sweden. No difference in gene expression was detected between any groups. Keywords: RNAseq, Gene expression profiles, Ethanol consumption, Rat.
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Project description:The nucleus accumbens core (NAcc) has been repeatedly demonstrated to be a key component of the circuitry associated with excessive ethanol consumption. Previous studies have illustrated that in a nonhuman primate (NHP) model of chronic ethanol consumption, there is significant epigenetic remodeling of the NAcc. In the current study, RNA-Seq was used to examine genome-wide gene expression in eight each of control, low/binge (LD*), and high/very high (HD*) rhesus macaque drinkers. Using an FDR < 0.05, zero genes were significantly differentially expressed (DE) between LD* and controls, six genes between HD* and LD*, and 734 genes between HD* and controls. Focusing on HD* versus control DE genes, the upregulated genes (N = 366) were enriched in genes with annotations associated with signal recognition particle (SRP)-dependent co-translational protein targeting to membrane (FDR < 3 × 10-59 ), structural constituent of ribosome (FDR < 3 × 10-47 ), and ribosomal subunit (FDR < 5 × 10-48 ). Downregulated genes (N = 363) were enriched in annotations associated with behavior (FDR < 2 × 10-4 ), membrane organization (FDR < 1 × 10-4 ), inorganic cation transmembrane transporter activity (FDR < 2 × 10-3 ), synapse part (FDR < 4 × 10-10 ), glutamatergic synapse (FDR < 1 × 10-6 ), and GABAergic synapse (FDR < 6 × 10-4 ). Ingenuity Pathway Analysis (IPA) revealed that EIF2 signaling and mTOR pathways were significantly upregulated in HD* animals (FDR < 3 × 10-33 and <2 × 10-16 , respectively). Overall, the data supported our working hypothesis; excessive consumption would be associated with transcriptional differences in GABA/glutamate-related genes.
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Project description:This is the first description of the effects of chronic ethanol consumption on the brain transcriptome in a non-human primate (rhesus macaque). Thirty male animals self-administered ethanol on a daily basis for over 12 months. Gene expression was measured with RNA-Seq in the central nucleus of the amygdala (CeA). Genes negatively correlated with consumption were enriched in functional annotations associated with translation and included clusters of ribosomal and mitochondrial ribosomal proteins. Genes positively correlated with consumption were enriched in membrane annotations including neuron and synapse part. Genes in the latter category included Ctnna2, Shank1, Vamp2, and Syn1. Gene-level expression data were clustered using the Weighted Gene Coexpression Network Analysis (WGCNA) algorithm to identify hub nodes affected by excessive consumption. Key hubs included Nf1, Nkain2, Tmem108 and Penk. The data were also analyzed for alternative exon usage (Iancu et al., 2015). Additional translation and membrane related genes affected by excessive consumption were detected. These included Grm2, Dpysl2 and Kcnc4. Overall, the data illustrate that the effects of excessive ethanol consumption are broad, consistent with the observation that ethanol affects the expression of numerous hub genes.
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Project description:On the Relationships in Rhesus Macaques between Chronic Ethanol Consumption and the Brain Transcriptome
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Project description:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naïve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included âÂÂnegative regulation of protein kinase activityâÂÂ, âÂÂanti-apoptosisâÂÂ, and âÂÂregulation of G-protein-coupled receptor protein signaling pathwayâÂÂ. Ingenuityî analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Experiment Overall Design: 10 samples each of control, continuous ethanol and limited access ethanol
2009-09-25 | E-GEOD-13524 | biostudies-arrayexpress
Project description:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naïve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included ‘negative regulation of protein kinase activity’, ‘anti-apoptosis’, and ‘regulation of G-protein-coupled receptor protein signaling pathway’. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Keywords: comparison of gene expression profiles for treated vs. control
2009-09-01 | GSE13524 | GEO
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Project description:This is the first description of the relationship between chronic ethanol self-administration and the brain transcriptome in a non-human primate (rhesus macaque). Twenty nine male animals self-administered ethanol on a daily basis for over 12 months. Gene transcription was quantified with RNA-Seq in the cortical Area 32. We constructed coexpression and cosplicing networks, and we identified areas of preservation and areas of differentiation between regions and network types. Correlations between intake and transcription included largely distinct gene sets and annotation categories across brain regions and between expression and splicing; positive and negative correlationswere also associated with distinct annotation groups. Our cosplicing analysis further identified the genes affected only at the exon inclusion level. In the Area 32 coexpression network, we identified a distinct hub set that included Ppp3r1 and Myeov2. Overall, the data illustrate that excessive ethanol self-administration is associated with broad expression and splicing mechanisms that involve membrane and synapse genes.
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