CCSER1 transcriptomic analysis reveals a role in neurodevelopmental phenotypes and alcohol response.
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE282155 | GEO | 2025/04/01
REPOSITORIES: GEO
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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:The National Institute on Alcohol Abuse and Alcoholism has estimated that approximately 14 million people in the United States suffer from alcoholism. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Whereas environmental factors, such as stress and social experience, contribute to individual variation in sensitivity to chronic alcohol consumption, genetic factors have also been implicated. However, genetic polymorphisms that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of olfactory sensitivity and, concomitant with development of tolerance, altered transcription of enzymes associated with fatty acid biosynthesis. Our results identify key enzymes in conserved metabolic pathways that may contribute to human alcohol sensitivity. Keywords: Drosophila, model system, alcohol sensitivity, tolerance
2006-07-27 | GSE5382 | GEO
Project description:Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL17 Receptor A (IL17ra-/-), or pharmacological blockade of IL17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice, and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL17A positively correlated with the alcohol use in excessive drinkers, and was further increased in patients with ALD as compared to healthy individuals. Our data suggest that IL17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL17A may provide a novel strategy for treatment of alcohol-induced pathology.
2020-04-07 | GSE137228 | GEO
Project description:MicroRNAs (miRNAs) are small non-coding RNAs with strong biological functions. However, the roles of miRNAs in alcohol addiction are still unclear. In this study, we analyzed miRNA profile of in the nucleus accumbens (NAc) of rats treated with alcohol. The results demonstrated, among the 300 detected miRNAs in NAc, multiple miRNAs were aberrantly expressed after treatment with alcohol.
2013-08-01 | GSE47943 | GEO
Project description:CCSER1 transcriptomic analysis reveals a role in neurodevelopmental phenotypes and alcohol response.
| PRJNA1187491 | ENA
Project description:MicroRNAs (miRNAs) are small non-coding RNAs with strong biological functions. However, the roles of miRNAs in alcohol addiction are still unclear. In this study, we analyzed miRNA profile of in the nucleus accumbens (NAc) of rats treated with alcohol. The results demonstrated, among the 300 detected miRNAs in NAc, multiple miRNAs were aberrantly expressed after treatment with alcohol. To perform the experiment, 18 male rats (weighing 150-180 g) were divided into two treatment groups: vehicle (500 ul saline, ip bid) or alcohol (1 g/kg, ip bid). Seven days later, the animals were sacrificed and their NAc were isolated for miRNA microarray analysis. The miRNA expressions were determined using miRNA microarrays for rat (LC Sciences). Data were normalized using cyclic method and statistically analyzed using Ttest.
2013-08-01 | E-GEOD-47943 | biostudies-arrayexpress
Project description:The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-naïve iP and P.NP rats. Background: Selectively bred P (alcohol preferring) and NP (alcohol non-preferring) rats differ greatly in alcohol preference, in part due to a highly significant QTL on chromosome 4. Reciprocal congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP background (NP.P) and the iNP chromosome 4 QTL was transferred to the iP background (P.NP) exhibited alcohol consumption scores that correlated with the introgressed interval. The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-naïve iP and P.NP rats. Methods: RNA from the amygdala, nucleus accumbens, hippocampus, caudate putamen, and frontal cortex from each of 8 iP and 8 P.NP rats was labeled and analyzed on Affymetrix Rat Genome 230 2.0 microarrays. Expression levels were normalized using robust multi-chip average (RMA), and differential gene expression was measured in individual brain regions and in the average of the five brain regions. Differential gene expression was validated using quantitative real-time PCR. Meta-analysis was applied to compare microarray data from this experiment with data from the reciprocal congenic strains NP.P vs. iNP (Carr et al, 2007). Results: We detected between 72 (nucleus accumbens) and 89 (hippocampus) cis-regulated probe sets within the QTL that significantly differed between the strains in the five brain regions. There was significant overlap among the regions; 157 cis-regulated probe sets were detected in at least one brain region, of which 104 showed differential expression in more than one region. Fewer trans-regulated probe sets were detected, ranging from 7 in the amygdala to 54 in the caudate putamen, and most of these differed in only one region; only 10 of the 85 trans-regulated probe sets differed in more than one region. To increase the power to detect differentially expressed genes, data from the five discrete brain regions of each animal were averaged; in this analysis we detected 141 cis-regulated probe sets and 207 trans-regulated probe sets. Meta-analysis comparing the present results from iP vs. P.NP rats with an earlier experiment that used the reciprocal congenic NP.P vs. iP demonstrated that 74 cis-regulated probe sets were differentially expressed in the same direction and with a consistent magnitude of difference in both experiments. No consistent trans-regulated probe sets were identified. Conclusions: Cis-regulated candidate genes for alcohol consumption that lie within the chromosome 4 QTL were identified and confirmed by meta-analysis with the reciprocal congenic NP.P vs iNP study. These genes are strong candidates for producing the difference in alcohol preference and consumption between the iP and iNP rats. There was little evidence for consistent trans-acting effects. Keywords: comparison of gene expression profiles for strain1 (P rat) vs. strain2 (P.NP rat) 40 samples each of P and P.NP (8 animals each of P and P.NP. 5 brain regions)
2009-12-30 | E-GEOD-15415 | biostudies-arrayexpress
Project description:A highly significant quantitative trait locus (QTL) that influenced alcohol preference was identified in the iP/iNP rats on chromosome 4. Congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP (NP.P) exhibited the expected increase in alcohol consumption compared to the iNP background strain. This study was undertaken to identify genes in the chromosome 4 QTL interval that might contribute to the differences in alcohol consumption between the alcohol-naïve congenic and background strains. RNA from five brain regions from each of 6 NP.P and 6 iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0 microarray. Expression levels were normalized using robust multi-chip average (RMA). Differential gene expression was validated using quantitative real-time PCR. An analysis combining five brain regions, including nucleus accumbens, frontal cortex, amygdala, hippocampus, and striatum, identified twenty three transcripts and nine ESTs that were differentially expressed between the NP.P and iNP. Of the twenty three observed transcripts, thirteen were known genes, 9 were predicted genes and all but one were located in the chromosome 4 QTL interval. Very interesting cis-regulated candidate genes for alcohol consumption were identified using microarray profiling of gene expression differences in congenic animals carrying a QTL for alcohol preference. Keywords: alcohol, congenic, rat, gene expression, brain, nucleus accumbens, amygdala, frontal cortex, hippocampus, striatum
2008-02-01 | GSE5849 | GEO
Project description:A highly significant quantitative trait locus (QTL) that influenced alcohol preference was identified in the iP/iNP rats on chromosome 4. Congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP (NP.P) exhibited the expected increase in alcohol; consumption compared to the iNP background strain. This study was undertaken to identify genes in the chromosome 4 QTL interval that might; contribute to the differences in alcohol consumption between the alcohol-naïve congenic and background strains. RNA from five brain regions; from each of 6 NP.P and 6 iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0 microarray. Expression levels; were normalized using robust multi-chip average (RMA). Differential gene expression was validated using quantitative real-time PCR. An analysis; combining five brain regions, including nucleus accumbens, frontal cortex, amygdala, hippocampus, and striatum, identified twenty three; transcripts and nine ESTs that were differentially expressed between the NP.P and iNP. Of the twenty three observed transcripts, thirteen; were known genes, 9 were predicted genes and all but one were located in the chromosome 4 QTL interval. Very interesting cis-regulated; candidate genes for alcohol consumption were identified using microarray profiling of gene expression differences in congenic animals carrying; a QTL for alcohol preference. Experiment Overall Design: Brain regions (accumbens, amygdala, frontal cortex, hippocampus, and striatum) from 6 biologic replicates of the selected non-preferring line NP and from a NP.P congenic line were dissected and subjected to microarray analysis for comparison.
2008-06-14 | E-GEOD-5849 | biostudies-arrayexpress
Project description:Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function. Here we focus on two genes deleted in a recurrent copy number variation causing neurodevelopmental disorders, the 22q11.2 microdeletion syndrome. We demonstrate that SLC25A1 and MRPL40, two genes present in the microdeleted segment and whose products localize to mitochondria, interact and are necessary for mitochondrial ribosomal integrity and proteostasis. Our Drosophila studies show that mitochondrial ribosome function is necessary for synapse neurodevelopment, function, and behavior. We propose that mitochondrial proteostasis perturbations, either by genetic or environmental factors, are a pathogenic mechanism for neurodevelopmental disorders.
2022-02-17 | PXD025289 | Pride