Withdrawal from chronic alcohol exposure leads to tissue-specific recovery of the zebrafish transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA600413 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10868200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10868200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10868201_1.fastq.gz | Fastqsanger.gz | |||
| SRR10868201_2.fastq.gz | Fastqsanger.gz | |||
| SRR10868202_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Alcohol consumption can lead to a wide-range of systemic disorders brought about by transcriptional changes. Recent studies have shown altered behavioral and expression changes in zebrafish on exposure to alcohol. We have identified changes associated with transcriptome profiles in response to chronic alcohol exposure and extent of recovery upon withdrawal. Our results indicate a tissue-specific response where the brain responds positively to withdrawal when compared to liver. We identified two distinct classes of genes in response to withdrawal from alcohol exposure – one group recovered the pre-exposure expression profile while the other set of genes retained altered expression profiles despite withdrawing from alcohol whose altered expression profiles remained changed even after withdrawal. We also examined gender-specific responses to alcohol. Male fish appear to be more susceptible to changes induced by alcohol indicated by a higher percent of genes appearing to change their expression profiles when compared to females. Female fish appear to show a better recovery as compared to males as a sizable number of genes appear to have their expression levels recovered upon the introduction of withdrawal. Overall, our work identifies pathways / genes perturbed by exposure to alcohol and demonstrates the extent of tissue-specific transcriptional changes and takes into account the variability of gender in assessing the effect of chronic alcoholism and withdrawal.
2020-10-09 | GSE143416 | GEO
Project description:Background and Purpose: Alcohol use disorder (AUD) is a serious public health issue and affects the lives of numerous people. Previous studies have shown a link between nicotinic acetylcholine receptors (nAChR) and alcohol addiction. However, the role of α6β2* nAChR in alcohol addiction remains obscure and whether α6β2* nAChR can be used as a potential drug target for alcohol withdrawal need to be studied. Methods: Zebrafish (Danio rerio) were exposed to 0.2% alcohol for 14 days followed by 7 days of repeated withdrawal and then retro-orbitally injected with α-conotoxin TxIB (a selective α6β2* nAChR antagonist). RNA-sequencing (RNA-seq) and subsequent bioinformatics analysis were applied to explore the potential network regulation by blocking α6β2* nAChR using TxIB after alcohol withdrawal. Results: RNA sequencing of zebrafish brain indicated a total of 657 genes showed aberrant expression and among which 225 were reversed after TxIB injection. These reversed genes were significantly enriched in cardiac muscle contraction and calcium signaling pathways and the gene expression profile was further validated by RT-PCR. Conclusion: Our finding suggests α6β2* nAChR antagonists have the potential to modulate alcohol withdrawal.
2021-11-03 | GSE186926 | GEO
Project description:Differential gene expression between mouse distal chromsome 1 congenic and background and reciprocal congenic and background Genetic factors significantly affect vulnerability to alcohol dependence (alcoholism). We previously identified a quantitative trait locus on chromosome 1 (Adw1) with a large effect on predisposition to alcohol physiological dependence and associated withdrawal following both chronic and acute alcohol exposure in mice. We fine-mapped these loci to a 1.1-1.7 Mb interval syntenic with human 1q23.2-23.3. Adw1 interval genes show remarkable genetic variation among mice derived from the C57BL/6J and DBA/2J strains, the two most widely studied genetic animal models for alcohol-related traits. Here, we report the creation of a novel recombinant Adw1 congenic model (R2) in which the Adw1 interval from a donor C57BL/6J strain is introgressed onto a uniform, inbred DBA/2J genetic background. As expected, R2 mice demonstrate significantly less severe alcohol withdrawal compared to wild-type littermates. Additionally, comparing R2 and background strain animals, as well as reciprocal congenic (R8) and appropriate background strain animals, we assessed Adw1 dependent brain gene expression using microarray and quantitative PCR analyses. To our knowledge this includes the first Weighted Gene Co-expression Network Analysis using reciprocal congenic models. Importantly, this allows detection of co-expression patterns limited to one or common to both genetic backgrounds with high and low predisposition to alcohol withdrawal severity. The gene expression patterns (modules) in common contain genes related to oxidative phosphorylation, building upon human and animal model studies that implicate involvement of oxidative phosphorylation in alcohol use disorders. Finally, we demonstrate that administration of N-acetylcysteine, an FDA-approved antioxidant, significantly reduces symptoms of alcohol withdrawal (convulsions) in mice, thus validating a phenotypic role for this network. Taken together, these studies support the importance of mitochondrial oxidative homeostasis in alcohol withdrawal and identify this network as a valuable therapeutic target in human alcohol use disorders.
2017-03-08 | GSE89281 | GEO
Project description:Glial cells are central players in the pathogenesis of neurodevelopmental disorders like Fetal Alcohol Spectrum Disorder (FASD). Ethanol can modulate glial differentiation and astrocyte function imposing dramatic changes to the developing brain. Since ethanol can affect a vast number of intracellular targets and signaling pathways and many effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to a long-lasting change in astrocyte secretome in vitro. Animals were treated every other day with ethanol (5g/kg) or saline between post-natal day (P)10-30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids (SILAC). 24h-conditioned media of cells obtained from ethanol- or saline-treated animals (ET-CM or SAL-CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET-CM to SAL-CM. Among 59 proteins found reduced in ET-CM we found components of the extracellular matrix like Laminin subunits α2, α4, β1, β2 and γ1 and the proteoglycans Biglycan, Heparin Sulfate Proteoglycan 2 and Lumican. Proteins with trophic function like Insulin-Like Growth Factor Binding Protein 4, Pigment Epithelium-Derived Factor and Clusterin as well as proteins involved on modulation of proteolysis like TIMP-1 and PAI-1 were also found reduced. On the other hand, pro-synaptogeneic proteins like Thrombospondin-1, Hevin as well as the modulator of extracelular matrix expression, Angiotensinogen, were found increased in ET-CM. The analysis of interactome maps through Ingenuity Pathway Analysis demonstrated that the Amyloid beta A4 protein precursor (APP), which was found reduced in ET-CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET-CM, rendering it a suitable target for a more accurate analysis about the effects of ethanol on its biology. Taken together our results strongly suggest that early exposure to teratogens such alcohol may lead to an enduring change in astrocyte secretome, affecting mainly the expression of trophic and matricellular proteins, which in turn may lead to permanent alterations in brain function.
2016-02-15 | PXD002787 | Pride
Project description:While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes. We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population. A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways weremore altered by alcohol. Examination of ethanol regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype. Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse.
2014-09-17 | GSE56249 | GEO
Project description:Alcohol is a psychoactive substance which has detrimental health effects upon consumption. Transcriptome profiling can provide insights into the dynamic changes in global gene expression profiles induced by chronic alcohol exposure and withdrawal. Male and female zebrafish were continually exposed to 0.5% ethanol for a period of 9 weeks. Upon completion of alcohol treatment, the fish were subjected to a withdrawal program for 9 weeks. Brain and liver tissues of control, alcohol exposed and withdrawal fish were isolated and the extracted RNA was sequenced on Illumina HiSeq 2000. The resultant paired end reads were mapped to the zebrafish reference genome (danRer10). The mapped transcripts were quantified for their expression and subjected to differential expression analysis across the three conditions. Gene ontology enrichment analysis of the differentially regulated genes was carried out to identify affected biological processes. The data for this project is available as a GEO dataset under Accession number GSE143416. The gene expression data discussed here accompanies the research article entitled 'Tissue-specific transcriptome recovery on withdrawal from chronic alcohol exposure in zebrafish'.
| S-EPMC7607250 | biostudies-literature
Project description:While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes. We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population. A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways weremore altered by alcohol. Examination of ethanol regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype. Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse. A total of 32 microarrays were run with 4 biological replicates per treatment, line, and sex. Selection replicates (i.e. WSP-1 and WSP-2) for each treatment, line, and sex were collapsed to improve statistical power (n=4) and to facilitate in the identification of phenotype related effects and exclude selection artifacts. For comparisons, EtOH regulation was determined by comparing 4 arrays from (for example) Male WSR EtOH treated versus 4 arrays from Male WSR Air treated arrays.
2014-09-17 | E-GEOD-56249 | biostudies-arrayexpress
Project description:α6β2* nAChR Antagonist TxIB Changed Gene Expression in Zebrafish (Danio rerio) brain Induced by Alcohol Withdrawal
| PRJNA776830 | ENA
Project description:The objective of The Center for Alcohol Research in Epigenetics (CARE) is to identify gene regulatory pathways in hippocampus that are altered in response to chronic ethanol administration and withdrawal.
2021-06-15 | GSE171051 | GEO
Project description:Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments. Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to chronic alcohol exposure (CAE), at different doses for 6 months followed by 1-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270 mM dose, CAE decreased cell viability by about 50% and 80%, respectively, in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of cancer stem cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3β signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly, we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies. Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-022-04387-y.
| S-EPMC9205837 | biostudies-literature