On the Relationships in Rhesus Macaques between Chronic Ethanol Consumption and the Brain Transcriptome
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ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE96732 | GEO | 2017/03/17
SECONDARY ACCESSION(S): PRJNA379471
REPOSITORIES: GEO
Similar Datasets
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). Thirty-one male animals self-administered ethanol on a daily basis for over 12 months. Gene transcription was quantified with RNA-Seq in the central nucleus of the amygdala (CeA) and 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 correlations were also associated with distinct annotation groups. Membrane, synaptic and splicing annotation categories were over-represented in the modules (gene clusters) enriched in positive correlations (CeA); our cosplicing analysis further identified the genes affected only at the exon inclusion level. In the CeA coexpression network, we identified Rab6b, Cdk18 and Igsf21 among the intake-correlated hubs, while in the Area 32, 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.
| S-EPMC5671907 | biostudies-literature
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.
2017-03-17 | GSE96731 | GEO
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.
2017-01-13 | GSE84332 | GEO
Project description:On the Relationships in Rhesus Macaques between Chronic Ethanol Consumption and the Brain Transcriptome
| PRJNA379471 | ENA
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.
| S-EPMC8588809 | biostudies-literature
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:It is well established that heavy ethanol consumption interferes with the immune system and inflammatory processes, resulting in increased risk for infectious and chronic diseases. However, these processes have yet to be systematically studied in a dose and sex-dependent manner. In this study, we investigated the impact of chronic heavy ethanol consumption on gene expression using RNA-seq in peripheral blood mononuclear cells isolated from female rhesus macaques with daily consumption of 4% ethanol available 22hr/day for 12 months resulting in average ethanol consumption of 4.3 g/kg/day (considered heavy drinking). Differential gene expression analysis was performed using edgeR and gene enrichment analysis using MetaCore™. We identified 1106 differentially expressed genes, meeting the criterion of ? two-fold change and p-value ? 0.05 in expression (445 up- and 661 down-regulated). Pathway analysis of the 879 genes with characterized identifiers showed that the most enriched gene ontology processes were "response to wounding", "blood coagulation", "immune system process", and "regulation of signaling". Changes in gene expression were seen despite the lack of differences in the frequency of any major immune cell subtype between ethanol and controls, suggesting that heavy ethanol consumption modulates gene expression at the cellular level rather than altering the distribution of peripheral blood mononuclear cells. Collectively, these observations provide mechanisms to explain the higher incidence of infection, delay in wound healing, and increase in cardiovascular disease seen in subjects with Alcohol use disorder.
| S-EPMC4948771 | biostudies-literature
Project description:Effect of Chronic Ethanol Consumption in Rhesus Macaques on the Nucleus Accumbens Core Transcriptome
| PRJNA604902 | ENA
Project description:Astrocytes play critical roles in central nervous system (CNS) homeostasis and are implicated in the pathogenesis of neurological and psychiatric conditions, including drug dependence. Little is known about the effects of chronic ethanol consumption on astrocyte gene expression. To address this gap in knowledge, we performed transcriptome-wide RNA sequencing of astrocytes isolated from the prefrontal cortex (PFC) of mice following chronic ethanol consumption. Differential expression analysis revealed ethanol-induced changes unique to astrocytes that were not identified in total homogenate preparations. Astrocyte-specific gene expression revealed calcium-related signaling and regulation of extracellular matrix genes as responses to chronic ethanol use. These findings emphasize the importance of investigating expression changes in specific cellular populations to define molecular consequences of chronic ethanol consumption in mammalian brain.
| S-EPMC6033697 | biostudies-literature
Project description:The mesolimbic dopamine system plays an important role in mediating a variety of behaviors and is involved in mediating the reinforcing effects of ethanol. Genes encoding dopamine receptor subtypes are thus good candidate loci for understanding the genetic etiologies of susceptibility to alcohol dependence and its antecedent behavioral phenotypes. We tested whether variation in DRD1 influences alcohol consumption in rhesus macaques and whether its influence is mediated by sex and early rearing experience. We genotyped a single nucleotide polymorphism (-111 G/T) in the 5'UTR of DRD1 in 96 subjects raised with their mothers until 6 months of age (n = 43) or in peer-only groups (n = 53). As young adults they underwent a 7-week voluntary ethanol consumption experiment. anova revealed a significant main effect of sex (F(1,95) = 6.3, P = 0.014) and an interaction between genotype, sex and rearing on ethanol consumption (F(7,95) = 4.63, P = 0.0002). Maternally deprived males heterozygous for the T allele consumed significantly more ethanol (P > t <or= 0.0001) than the other subgroups. Maternal deprivation can produce individuals that are anxious and impulsive, both of which are known risk factors for alcohol dependence. Our work demonstrates a potential role for the dopamine D1 receptor gene in modulating alcohol consumption, especially in the context of early environmental stress.
| S-EPMC2880628 | biostudies-literature