Comparison of small RNA-seq and microarray analysis for determining the effects of acute prenatal ethanol exposure on microRNA expression and its amelioration by environmental manipulation
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Rattus norvegicus
PROVIDER: GSE60901 | GEO | 2014/08/29
SECONDARY ACCESSION(S): PRJNA259765
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-29 | E-GEOD-60901 | biostudies-arrayexpress
Project description:In this study, we tested if miRNAs are altered in amygdala and ventral striatum as a consequence of prenatal ethanol exposure and/or social enrichment. miRNA samples from 72 male and female adolescent rats were analyzed by RNA-Seq analysis and Affymetrix miRNA arrays. Several miRNAs showed significant changes due to prenatal ethanol exposure or social enrichment in one or both brain regions. Some of the miRNA changes caused by ethanol were reversed by social enrichment. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. We also directly examined the evidence for modulation of target mRNAs in whole transcriptome microarray data from the same rats. Among the pathways most strongly affected were p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure. A total of 48 samples were analyzed by small RNA-Sequencing using RNA purified from 2 brain regions (amygdala and ventral striatum) of postnatal day 42 Long Evans rats. 3 replicate sequencing runs were performed for each gender within 4 different treatment groups (prenatal ethanol or prenatal saline exposed; postnatal socially-enriched or non-enriched environment)
2014-08-29 | E-GEOD-60900 | biostudies-arrayexpress
Project description:In this study, we tested if miRNAs are altered in amygdala and ventral striatum as a consequence of prenatal ethanol exposure and/or social enrichment. miRNA samples from 72 male and female adolescent rats were analyzed by RNA-Seq analysis and Affymetrix miRNA arrays. Several miRNAs showed significant changes due to prenatal ethanol exposure or social enrichment in one or both brain regions. Some of the miRNA changes caused by ethanol were reversed by social enrichment. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. We also directly examined the evidence for modulation of target mRNAs in whole transcriptome microarray data from the same rats. Among the pathways most strongly affected were p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure. A total of 48 Rat ST Gene 1.0 GeneChips and 48 miRNA 2.0 GeneChips were run on RNA purified from 2 brain regions (amygdala and ventral striatum) of postnatal day 42 Long Evans rats. 3 replicate arrays were run for each gender within 4 different treatment groups (prenatal ethanol or prenatal saline exposed; postnatal socially-enriched or non-enriched environment)
2014-08-28 | E-GEOD-60819 | biostudies-arrayexpress
Project description:In this study, we tested if miRNAs are altered in amygdala and ventral striatum as a consequence of prenatal ethanol exposure and/or social enrichment. miRNA samples from 72 male and female adolescent rats were analyzed by RNA-Seq analysis and Affymetrix miRNA arrays. Several miRNAs showed significant changes due to prenatal ethanol exposure or social enrichment in one or both brain regions. Some of the miRNA changes caused by ethanol were reversed by social enrichment. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. We also directly examined the evidence for modulation of target mRNAs in whole transcriptome microarray data from the same rats. Among the pathways most strongly affected were p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure.
2014-08-28 | GSE60819 | GEO
Project description:In this study, we tested if miRNAs are altered in amygdala and ventral striatum as a consequence of prenatal ethanol exposure and/or social enrichment. miRNA samples from 72 male and female adolescent rats were analyzed by RNA-Seq analysis and Affymetrix miRNA arrays. Several miRNAs showed significant changes due to prenatal ethanol exposure or social enrichment in one or both brain regions. Some of the miRNA changes caused by ethanol were reversed by social enrichment. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. We also directly examined the evidence for modulation of target mRNAs in whole transcriptome microarray data from the same rats. Among the pathways most strongly affected were p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure.
2014-08-29 | GSE60900 | GEO
Project description:BackgroundAs part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we performed a DNA microarray analysis of human whole blood samples from a five-time point study of subjects administered ethanol orally, followed by breathalyzer analysis, to monitor blood alcohol concentration (BAC) to discover significant gene expression changes in response to the ethanol exposure.MethodsSubjects were administered either orange juice or orange juice with ethanol. Blood samples were taken based on BAC and total RNA was isolated from PaxGene™ blood tubes. The amplified cDNA was used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR) analyses to evaluate differential gene expression. Microarray data was analyzed in a pipeline fashion to summarize and normalize and the results evaluated for relative expression across time points with multiple methods. Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. RT-qPCR was used with representative genes to confirm relative transcript levels across time to those detected in microarrays.ResultsMicroarray analysis of samples representing 0%, 0.04%, 0.08%, return to 0.04%, and 0.02% wt/vol BAC showed that changes in gene expression could be detected across the time course. The expression changes were verified by qRT-PCR.The candidate genes of interest (GOI) identified from the microarray analysis and clustered by expression pattern across the five BAC points showed seven coordinately expressed groups. Analysis showed function-based networks, shared transcription factor binding sites and signaling pathways for members of the clusters. These include hematological functions, innate immunity and inflammation functions, metabolic functions expected of ethanol metabolism, and pancreatic and hepatic function. Five of the seven clusters showed links to the p38 MAPK pathway.ConclusionsThe results of this study provide a first look at changing gene expression patterns in human blood during an acute rise in blood ethanol concentration and its depletion because of metabolism and excretion, and demonstrate that it is possible to detect changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study serves as a workflow to investigate the biology linked to expression changes across a time course and from these changes, to identify target genes that could serve as biomarkers linked to pilot performance.
| S-EPMC3750403 | biostudies-literature
Project description:BackgroundNeuroinflammation is a widely studied phenomenon underlying various neurodegenerative diseases. Earlier study demonstrated that pharmacological activation of GPR110 in both central and peripheral immune cells cooperatively ameliorates neuroinflammation caused by systemic lipopolysaccharide (LPS) administration. Ethanol consumption has been associated with exacerbation of neurodegenerative and systemic inflammatory conditions. The goal of this study is to determine the effects of single-dose acute ethanol exposure and GPR110 activation on the neuro-inflammation mechanisms.MethodsFor in vivo studies, GPR110 wild type (WT) and knockout (KO) mice at 10-12 weeks of age were given an oral gavage of ethanol (3 g/kg) or maltose (5.4 g/kg) at 1-4 h prior to the injection of LPS (1 mg/kg, i.p.) followed by the GPR110 ligand, synaptamide (5 mg/kg). After 2-24 h, brains were collected for the analysis of gene expression by RT-PCR or protein expression by western blotting and enzyme-linked immunosorbent assay (ELISA). Microglial activation was assessed by western blotting and immunohistochemistry. For in vitro studies, microglia and peritoneal macrophages were isolated from adult WT mice and treated with 25 mM ethanol for 4 h and then with LPS (100 ng/ml) followed by 10 nM synaptamide for 2 h for gene expression and 12 h for protein analysis.ResultsSingle-dose exposure to ethanol by gavage before LPS injection upregulated pro-inflammatory cytokine expression in the brain and plasma. The LPS-induced Iba-1 expression in the brain was significantly higher after ethanol pretreatment in both WT and GPR110KO mice. GPR110 ligand decreased the mRNA and/or protein expression of these cytokines and Iba-1 in the WT but not in GPR110KO mice. In the isolated microglia and peritoneal macrophages, ethanol also exacerbated the LPS-induced expression of pro-inflammatory cytokines which was mitigated at least partially by synaptamide. The expression of an inflammasome marker NLRP3 upregulated by LPS was further elevated with prior exposure to ethanol, especially in the brains of GPR110KO mice. Both ethanol and LPS reduced adenylate cyclase 8 mRNA expression which was reversed by the activation of GPR110. PDE4B expression at both mRNA and protein level in the brain increased after ethanol and LPS treatment while synaptamide suppressed its expression in a GPR110-dependent manner.ConclusionSingle-dose ethanol exposure exacerbated LPS-induced inflammatory responses. The GPR110 ligand synaptamide ameliorated this effect of ethanol by counteracting on the cAMP system, the common target for synaptamide and ethanol, and by regulating NLRP3 inflammasome.
| S-EPMC10426059 | biostudies-literature
Project description:Fetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs) are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of social enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or social enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by social enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p, and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, glutamate, and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression.
| S-EPMC4173670 | biostudies-literature
Project description:BackgroundIndividuals with fetal alcohol spectrum disorders (FASD) often show processing deficits in all sensory modalities. Using an operant light reinforcement model, we tested whether prenatal ethanol exposure (PE) alters operant responding to elicit a contingent sensory stimulus-light onset (turning on the light) and habituation to this behavior in rats. We also explored whether postnatal environmental enrichment could ameliorate PE-induced deficits.MethodsPregnant Sprague Dawley rats were gavaged twice/day with 0 or 3 g/kg/treatment ethanol (15% w/v) during gestational days 8-20, mimicking second-trimester heavy PE in humans. The offspring were reared in a standard housing condition or an enriched condition. Adult male and female offspring underwent an operant light reinforcement experiment with either a short-access or a long-access procedure. A dishabituation test was also conducted to characterize the habituation process.ResultsIn the short-access procedure, PE led to increased operant responding to the contingent light onset in both sexes reared in the standard housing condition. Such an effect was not observed in rats reared in enriched conditions due to an overall decrease in responding. Moreover, rats reared in enriched conditions showed greater short-term habituation. In the long access procedure, PE rats showed increased responding and impaired long-term habituation. The long-access procedure facilitated both short-term and long-term habituation in control and PE rats.ConclusionPrenatal ethanol exposure increases responding to contingent light onset and impairs the long-term habituation process. The PE-induced deficits were ameliorated by rearing in the enriched environment and increasing the duration and frequency of exposure to light onset. The PE-induced effects are like increased sensation-seeking, a subtype of sensory-processing deficit that is often observed in individuals with FASD. Our findings could inform a suitable animal model for investigating the underlying mechanisms and possible intervention strategies for sensory deficits in FASD.
| S-EPMC9122102 | biostudies-literature
Project description:As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we present results of our DNA microarray analysis of samples from a timecourse study of individuals given ethanol orally, and then evaluated by breathalyzer to monitor blood alcohol content (BAC). At five blood alcohol levels, T1-T5, blood was drawn such that the samples represented 0%, 0.04%, 0.08% BAC, and return to 0.04%, and 0.02% BAC. Microarray analysis showed that changes in gene expression could be detected across the time-course. We verified these expression changes by quantitative polymerase chain reaction (qPCR). Candidate target genes identified from the microarray analysis were clustered by expression change pattern, examined for shared functions and functional network membership. Five coordinately expressed groups were revealed and functional analysis showed shared transcription factor binding sites and functions for members of the clusters. These functions include protein synthesis and modification, expected for changes in gene expression, hematological and immune functions, expected for a blood sample, and pancreatic and hepatic function, expected as response to ethanol. The results provide a first look at changing gene expression patterns in blood during acute increase of ethanol concentration and its depletion due to metabolism or excretion and demonstrate that it is possible to detect significant changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study can be utilized as part of a workflow to identify target genes by timecourse changes in gene expression that may affect pilot performance.
2013-07-25 | GSE20489 | GEO