α6β2* nAChR Antagonist TxIB Changed Gene Expression in Zebrafish (Danio rerio) brain Induced by Alcohol Withdrawal
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ABSTRACT:
PROVIDER: PRJNA776830 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16676615_1.fastq.gz | Fastqsanger.gz | |||
| SRR16676615_2.fastq.gz | Fastqsanger.gz | |||
| SRR16676616_1.fastq.gz | Fastqsanger.gz | |||
| SRR16676616_2.fastq.gz | Fastqsanger.gz | |||
| SRR16676617_1.fastq.gz | Fastqsanger.gz |
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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: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: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: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:The objective of The Center for Alcohol Research in Epigenetics (CARE) is to identify gene regulatory pathways in ventral tegmental area (VTA) that are altered in response to chronic ethanol administration and withdrawal.
2024-02-15 | GSE233921 | GEO
Project description:Withdrawal from chronic alcohol exposure leads to tissue-specific recovery of the zebrafish transcriptome
| PRJNA600413 | ENA
Project description:Rats were trained to orally self-administer alcohol in a concurrent, two-lever, free-choice contingency using a modification of the sweet solution fading procedure (O'Dell et al., 2004; Roberts et al., 2000; Vendruscolo et al., 2012). Following acquisition of self-administration, rats were allowed to self-administer unsweetened alcohol (10%) for 4 weeks and were then assigned to two groups matched by levels of responding: one group (dependent group) was exposed to chronic, intermittent ethanol vapors for 4 weeks to induce dependence; the other group (nondependent group) was not exposed to ethanol vapor. After a month of vapor exposure, rats were again tested during acute withdrawal (6-8 hours after removal from the vapor chambers) until stable levels of alcohol intake were achieved. As expected, alcohol vapor-exposed rats self-administered significantly greater amounts of alcohol than control rats not exposed to alcohol vapor during acute withdrawal. Rats were sacrificed during protracted abstinence (3 weeks after the end of alcohol vapor exposure) along with age-matched alcohol naive rats.
2014-11-13 | GSE60966 | GEO
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:Background Chronic preconception paternal alcohol use modifies the sperm epigenome, inducing fetoplacental growth defects in the offspring of exposed males. A crucial outstanding question in the field of paternal epigenetic inheritance concerns the resilience of the male reproductive tract and the germline's capacity to recover and correct sperm-inherited epigenetic errors after stressor withdrawal. Objectives We set out to determine if measures of the sperm-inherited epigenetic program revert to match the control treatment one month after withdrawing daily alcohol treatments. Materials and Methods Using a voluntary access model, we exposed C57Bl6/J males to 10% alcohol for ten weeks, withdrew alcohol treatment for four weeks, and used RNA sequencing to examine gene expression patterns in the caput section of the epididymis. We then compared the abundance of sperm small RNA species between treatments. Results In the caput section of the epididymis, chronic alcohol exposures induced changes in the transcriptional control of genetic pathways related to mitochondrial function, oxidative phosphorylation, the generalized stress response (EIF2 signaling), and Sirtuin signaling. Subsequent analysis identified region-specific, alcohol-induced changes in mitochondrial DNA copy number across the epididymis, which correlated with increases in the mitochondrial DNA content of alcohol-exposed sperm. Notably, in the corpus section of the epididymis, increases in mitochondrial DNA copy number persisted one month after alcohol cessation. Analysis of sperm noncoding RNAs between Control and Alcohol-Exposed males one month after alcohol withdrawal revealed a ~100-fold increase in mir-196a, a microRNA induced as part of the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-driven cellular antioxidant response. Discussion and Conclusion Our data reveal that alcohol-induced epididymal mitochondrial dysfunction and differences in sperm noncoding RNA content persist after alcohol withdrawal. Further, differences in mir-196a and sperm mitochondrial DNA copy number may serve as viable biomarkers of adverse alterations in the sperm-inherited epigenetic program.
2023-06-13 | GSE234535 | GEO