Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: Comparison with immune activation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE42789 | GEO | 2013/04/01
SECONDARY ACCESSION(S): PRJNA183349
REPOSITORIES: GEO
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Project description:We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes in brain and liver among three different alcohol consumption tests and lipopolysaccharide injection. We also demonstrated distinct genomic consequences of different types of alcohol consumption. The microarray experiment was performed to compare gene expression changes induced by three separate paradigms of alcohol consumption and immune activation by lipopolysaccharide injection. The three tests of alcohol consumption were the continuous chronic two bottle choice (Chronic), two bottle choice available every other day (Chronic Intermittent) and limited access to one bottle of ethanol (Drinking in the Dark). All alcohol studies utilized 20% ethanol and each treatment group had it's own control group which received only water. The immune activation test consisted of 2 lipopolysaccharide injections (1 mg/kg i.p.) spaced one week apart, with animals being sacrificed one week after the last injection. Control animals received saline injections. All studies used female, adult mice.
2013-04-01 | E-GEOD-42789 | biostudies-arrayexpress
Project description:Chronic and binge ethanol consumption in humans and in animal models has been associated with the induction of injury (such as fibrosis and scarring) in the liver as well as the intestine, brain, lung and immune system. The effects of chronic ethanol consumption on the human kidney are protective as seen in large population studies are controversial with the preponderance of the data suggesting protection less so than injury. The most recent meta-analysis was by Konig et al (2015) who studied 5476 participants aged 28–75 years from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study to assess associations between alcohol consumption and risk of chronic kidney disease (CKD). They found in this population-based cohort, alcohol consumption was inversely associated with the risk of developing CKD. The protective effects of ethanol on the kidney present a unique model system to develop new hypothesis on protection against end organ damage by fibrosis. The data on the effects of alcohol or alcohol consumption at the molecular level on renal parenchyma are sparse. In cell culture and animal models chronic ethanol exposure has been show to induce protein post-translational modification (acetylation), protein expression (upregulation of cytochrome P450 CYP2E1 and local platelet-activating factor receptor (PAFR) ligand formation) as well as neutrophil infiltration and activation. Since hepatocytes do not express PAFR, these data suggest that the response of the kidney to chronic alcohol consumption is distinct from that of the liver or lung. Therefore, we hypothesized that mechanisms of ethanol-induced renal injury or protection are regulated by a protein signaling networks (PSN) modulated acutely by the phosphoproteome and long term epigenetically by the acetylproteome. To address this hypothesis we have initiated a tiered proteomics study to determine the effects of chronic alcohol consumption on the murine kidney and with a secondary insult of acute exposure of lipopolysaccharide (LPS) on the renal proteome, phosphoproteome and the acetylproteome. Data have already been collected on the total proteome and the phosphoproteome using a multiplexing approach. Data will be collected early spring on the acetylproteome.
2019-05-15 | GSE81947 | GEO
Project description:Accumulating evidence suggests that lifestyle-related factors may influence radiation responses and the resulting cancer risks through epigenetic mechanisms, such as miRNA regulations. Chronic alcohol consumption is a major risk factor for various pathologies, including alcoholic liver disease. We have recently shown that consumption of Japanese sake promotes glutathione metabolism and anti-oxidative activities in the liver of irradiated C57BL/6 mice. Here we show that chronic alcohol consumption resulted in elevated ciculating levels of the inflammatory cytokine TNF-α and that it triggered specific miRNA regulations (such as the upregulation of the radio-resistant miR-210) that are susceptible to influence the resulting radiation effects in the mouse liver.
2016-03-15 | GSE79186 | GEO
Project description:Accumulating evidence suggests that lifestyle-related factors may influence radiation responses and the resulting cancer risks through epigenetic mechanisms, such as miRNA regulations. Chronic alcohol consumption is a major risk factor for various pathologies, including alcoholic liver disease. We have recently shown that consumption of Japanese sake promotes glutathione metabolism and anti-oxidative activities in the liver of irradiated C57BL/6 mice. Here we show that chronic alcohol consumption resulted in elevated ciculating levels of the inflammatory cytokine TNF-α and that it triggered specific miRNA regulations (such as the upregulation of the radio-resistant miR-210) that are susceptible to influence the resulting radiation effects in the mouse liver. Japanese sake was administrated to C3H mice irradiated with 3 Gy X-rays. miRNA expression was measured in the livers of 3 mice for each experimental group.
2016-03-15 | E-GEOD-79186 | biostudies-arrayexpress
Project description:Analysis of transcriptiomic alternations related with alcohol use disorders (AUDs). The hypothesis is that chronic alcohol consumption might alter genome-wide gene expression patterns. The results suggest that differential gene expression in the prefrontal cortex is implicated in neuroadaptations to alcohol. Total RNAs were extracted from postmortem prefrontal cortex tissues from 23 AUD cases and 23 matched controls. Both AUD cases and matched controls were assessed with DSM-IV.
2013-11-06 | E-GEOD-49376 | biostudies-arrayexpress
Project description:Action of alcohol on synaptic mRNA in the amygdala of mice Chronic alcohol consumption induces changes in gene expression, causing persistent long-term neuro-adaptations and the remodeling of synaptic structures. These alcohol-induced synaptic changes may rely specifically on the local translation of mRNAs in the synaptic compartments of the cell. We profiled the transcriptome from synaptoneurosomes (SN) and paired total homogenates (TH) of amygdala to analyze the synaptic adaptations induced by chronic voluntary alcohol consumption in mice. In the SN both the number of alcohol-responsive mRNAs and the magnitude of fold-change were greater than in the TH. Accordingly, the SN detected many genes with coordinated patterns of expression producing a highly connected mRNA network in gene co-expression analysis. The greater sensitivity of the SN preparation allowed for improved cell-type specificity analysis, revealing an up-regulation of alcohol-responsive astrocytic and microglial modules that correlated with alcohol consumption. Alcohol was found to induce changes in the SN functionally important biological pathways, including long-term potentiation, long-term potentiation depression, glutamate pathway, neuro-immune, RNA-processing and translational machineries and provided overlap with changes seen in human alcoholic brain. Transposable elements were responsive to alcohol and found in the down-regulated neuronal mRNA module, which may underlie some of the coordinated gene expression changes associated with alcohol. We provide evidence that enrichment of synaptic components reveals a more intricate network of coordinated gene expression. Increased resolution captures the molecular effects of synaptic manipulations and provides an improved technique for identifying therapeutic targets for alcohol abuse. Synaptoneurosomes (SN) and Paired total homogenates (TH) were prepared from the same homogenate. 42 microarrays were used in total for the alcohol-control analysis (8 alcohol treated mice and 13 controls), 21 SN and 21 paired TH. 2 TH (control) samples were found outliers and were removed from the analysis. For the SN vs. TH analysis, the 2 TH samples found outliers were removed with the 2 paired SN samples.
2013-10-28 | E-GEOD-51730 | biostudies-arrayexpress
Project description:Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated microglia in response to recurring bouts of voluntary alcohol drinking behavior. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Several genes in this group were involved in toll-like receptor signaling and production of the inflammatory cytokine interferon-gamma. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. We identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, as well as related CNS disorders.
2016-12-10 | GSE91387 | GEO
Project description:Analysis of transcriptiomic alternations related with alcohol use disorders (AUDs). The hypothesis is that chronic alcohol consumption might alter genome-wide gene expression patterns. The results suggest that differential gene expression in the prefrontal cortex is implicated in neuroadaptations to alcohol.
2013-11-06 | GSE49376 | GEO
Project description:Purpose: Traditional whole-tissue sequencing approaches do not fully capture brain cell-type specific effects of chronic alcohol. Therefore, the purpose of this study was to identify the specific transcriptome alterations in astrocytes due to chronic alcohol. Methods: We performed RNA-sequencing on astrocytes isolated from the prefrontal cortex (PFC) of C57BL/6J mice following chronic every-other-day alcohol consumption. Results: Differential expression analysis revealed alcohol-induced gene expression changes unique to astrocytes that could not be identified using whole tissue homogenate analysis. Enrichment analysis revealed involvement of calcium-related signaling and regulation of extracellular matrix genes in the astrocyte response to alcohol abuse. Conclusion: Our study presents the first focused analysis on the astrocyte transcriptome following chronic alcohol consumption, provides a framework for studying the functional response of astrocytes to alcohol and the possible astrocyte-specific effects of alcohol. In addition, our data represents a novel resource for groups interested in biological functions of astrocytes in the adult mouse PFC.
2018-01-10 | GSE92457 | GEO
Project description:Analysis of methylomic alternations related with alcohol use disorders (AUD). The hypothesis is that chronic alcohol consumption might alter genome-wide DNA methylation patterns. The results suggest that differential DNA methylation might be invovled in neuradaptations to alcohol. Genomic DNA was extraced from postmortem prefrontal cortex tissues of 23 AUD cases and 23 matched controls. Both AUD cases and matched controls are assessed with DSM-IV
2013-11-06 | E-GEOD-49393 | biostudies-arrayexpress