Dysregulation of miRNA regulatory networks by chronic ethanol consumption impairs liver regeneration
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PROVIDER: PRJNA719565 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we elucidated the role of miRNA dysregulation in liver regeneration after partial hepatectomy (PHx) in chronic ethanol-treated rats. Male Sprague-Dawley rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced by carbohydrate. After 5 weeks, locked nucleic acid (LNA)-modified oligo antisense to miR-21 (AM21, Exiqon) was used to inhibit miRNA in vivo, and rats were subjected to 70% PHx. Liver samples were collected at 6 h, 24 h and 72 h after the surgery. The excised liver samples at t=0 served as within-animal controls.NanoString rat miRNA panel was used to obtain miRNA expression profile from 48 liver samples.
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Project description:In recent years, varenicline has been shown to decrease ethanol consumption in adult rodents providing support as a therapeutic treatment for alcohol use disorder (AUD). Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors, but interacts with other receptors at high concentrations. In order to gain a greater understanding of the mechanisms by which varenicline decreases ethanol consumption, we performed RNA sequencing on striatal tissue from C57BL/6J mice treated with varenicline or saline prior to an ethanol Drinking-in-the-Dark (DID) session. Using classical tools to analyze RNA sequencing data, we found 809 differentially expressed genes with Cuffdiff and one significant co-expression network using WGCNA.
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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.
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Project description:We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring. Pregnant Long-Evans rats voluntarily consumed either a 0% or 5% ethanol solution four hours each day throughout gestation. Ethanol consumption produced a mean maternal daily intermittent peak serum ethanol concentration of 84 mg/dL. Placentas were harvested on Gestational Day 20 for gene expression studies.
2010-02-21 | E-GEOD-18162 | biostudies-arrayexpress
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.
2017-06-01 | GSE73627 | 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:Of the more than 100 studies that have examined some aspect of the relationships between excessive ethanol consumption and the brain transcriptome, relatively few rodent studies have examined the effects of chronic consumption. The current study allowed 114 heterogeneous stock collaborative cross mice to freely consume 10% ethanol for 3 months (13 weeks), with a water choice. RNA-Seq data were then used to identify transcriptional differences within the central nucleus of the amygdala, a brain region known to impact ethanol preference. Average week 1 preference for consuming ethanol over water was modestly correlated with average preference for the final week of the study, and over the course of the 3-month trial, a sex-difference emerged. In females but not males, there was a significant escalation of preference from week 1 to week 13 and significant alignment of the transcriptome with average week 13 ethanol preference and consumption was found for female, but not male mice. The genes significantly correlated with preference were enriched in annotations associated with cilium movement, cilium organization, extracellular region and collagen-containing extracellular matrix. For the females, 376 of the total 415 genes that correlated with ethanol preference in the gene co-expression network were associated with a single network module that was enriched in genes with an astrocyte annotation. The key hub node in the module was the master regulator, orthodenticle homeobox 2 (Otx2). These data support an important role for the extracellular matrix and primary cilium in individual differences in ethanol preference and consumption in a genetically diverse population of mice.
2020-05-29 | GSE151410 | GEO
Project description:Despite recent extensive genomic and genetic studies on behavioral responses to ethanol, relatively few new therapeutic targets for the treatment of alcohol use disorder have been validated. Here we describe a cross-species genomic approach focused on identifying gene networks associated with chronic ethanol consumption. To identify brain mechanisms underlying a chronic ethanol consumption phenotype highly relevant to human alcohol use disorder, and to elucidate potential future therapeutic targets, we conducted a genomic study in a nonhuman primate model of chronic open-access ethanol consumption. Microarray analysis of RNA expression in anterior cingulate and subgenual cortices from rhesus macaques was performed across multiple cohorts of animals. Gene networks correlating with ethanol consumption or showing enrichment for ethanol-regulated genes were identified, as were major ethanol-related hub genes within these networks. A subsequent consensus module analysis was used to co-analyze monkey data with expression data from a chronic intermittent ethanol vapor-exposure and consumption model in C57BL/6J mice. Ethanol-related gene networks conserved between primates and rodents were enriched for genes involved discrete biological functions, including; myelination, synaptic transmission, chromatin modification, Golgi apparatus function, translation, cellular respiration, and RNA processing. The myelin-related network, in particular, showed strong correlations with ethanol consumption behavior and displayed marked network reorganization between control and ethanol-drinking animals. Further bioinformatics analysis revealed that these networks also showed highly significant overlap with other ethanol-regulated gene sets. Altogether, these studies provide robust primate and rodent cross-species validation of gene networks associated with chronic ethanol consumption. Our results also suggest potential novel focal points for future therapeutic interventions in alcohol use disorder.
2019-09-03 | GSE134546 | GEO
Project description:In this study, we analyzed the effects of chronic alcohol consumption on liver repair and regeneration after partial hepatectomy (PHx). Rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced either by carbohydrate or by fat. After 5 weeks, rats were subjected to 70% PHx and liver samples were collected at 1, 6 and 24h after the surgery. The excised liver samples at t=0 served as within-animal controls. We used Affymetrix Rat Gene 1.0 ST arrays to obtain global gene expression data from each liver sample (n=4 replicate rats, 72 arrays total).
2012-07-24 | GSE33785 | GEO
Project description:Male Wistar rats weighing 90-120 g were acclimatized for one week and fed standard laboratory chow, at which time the animals were divided into two groups. Animals were then pair-fed for 8 weeks a regular laboratory chow and water “ad libitum” or Lieber-DeCarli diet (36% calories from ethanol). Control animals received the iso-caloric amount of dextrose to replace ethanol. After 8 weeks of differential feeding rats were euthanized, the pancreas immediately dissected and stored at -80?C until RNA isolation. RNA expression was analyzed using Affymetrix RAE230A gene chips Keywords: stress response, disease state analysis
2006-07-01 | GSE3311 | GEO