Alcohol-induced anxiolysis is mediated through inhibition of microRNA-494 expression in the amygdala
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE68278 | GEO | 2016/11/29
SECONDARY ACCESSION(S): PRJNA282373
REPOSITORIES: GEO
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Project description:RNA-sequencing of adult rat amygdala tissue following acute ethanol treatment, compared to saline-treated controls.
2022-09-22 | GSE171400 | GEO
Project description:ATAC-sequencing of adult rat amygdala tissue following acute ethanol treatment, compared to saline-treated controls.
2022-09-22 | GSE171399 | GEO
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 to 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in the central nucleus of the amygdala (CeA) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.
2013-07-20 | E-GEOD-49040 | biostudies-arrayexpress
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function.
2013-07-20 | GSE49040 | GEO
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like drinking by alcohol-preferring (P) rats. Adult male P rats were given 1-hr access to 15 and 30% ethanol (EtOH) three times daily for 8 weeks. Rats (n = 10/time point for EtOH and n = 6/time point for water) were killed by decapitation 1, 6 and 24 hr after the last drinking episode. Brains were extracted and rapidly frozen in isopentane in dry ice. RNA was prepared from individual micropunch samples of the nucleus accumbens shell (ACB-sh) and central nucleus of the amygada (CeA); microarray analyses were conducted with Affymetrix Rat 230.2 chips. EtOH intakes were 1.5-2 g/kg/session. Because too few genes changed at the individual time points, an overall effect, comparing the water and EtOH groups, was determined. In the ACB-sh and CeA, there were 276 and 402 probe sets for named genes, respectively, that were different between the two groups. There were 1.5- to 3.5- fold more genes up-regulated than down-regulated in both regions, with most differences between 1.1- to 1.2-fold. Although there were several significant Biological Processes categories in common between the 2 regions (e.g., synaptic transmission, neurite development), there were few genes in common between the two regions that differed between the EtOH and water groups. Overall, the results suggest that chronic binge-like alcohol drinking by P rats produces changes in the expression of genes that could alter neuronal function by different mechanisms in the ACB-sh and CeA. 17 samples of control and 31 samples of treatment for each brain region
2009-12-30 | E-GEOD-15407 | biostudies-arrayexpress
Project description:Repeated excessive alcohol consumption is a risk factor for alcohol use disorder (AUD). Although AUD has been more common in men than women, women develop more severe behavioral and physical impairments. However, relatively few new therapeutics targeting development of AUD have been validated. Here, to gain a better understanding of molecular mechanisms underlying alcohol intake, we conducted a genome-wide RNA-sequencing analysis in female mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in amygdala including the central and basolateral subnuclei, brain areas previously implicated in alcohol drinking and seeking. We found distinct gene expression patterns and canonical pathways induced by both acute and chronic intake. Surprisingly, both drinking modes triggered similar transcriptional changes, including up-regulation of ribosome-related/translational pathways and myelination pathways, and down-regulation of chromatin binding and histone modification. Notably, multiple genes that were significantly altered with alcohol drinking, including Atp2b1, Hspa4, Slc4a7, Sbno1, Ubxn2b, Nfkb1, Nts, and Hdac2, had previously been associated with human AUD via GWAS or other genomic studies. In addition, subsequent analyses of hub genes and upstream regulatory pathways predicted that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and the oligodendrocyte-related transcription factor, Sox17. Overall, our results suggest that the expression of oligodendrocyte-related genes in the central and basolateral subnuclei of the amygdala is sensitive to voluntary alcohol drinking. These findings suggest potential molecular targets for future therapeutic approaches to prevent the development of AUD, particularly in women, due to repeated excessive alcohol consumption
2022-11-28 | GSE208014 | GEO
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like drinking by alcohol-preferring (P) rats. Adult male P rats were given 1-hr access to 15 and 30% ethanol (EtOH) three times daily for 8 weeks. Rats (n = 10/time point for EtOH and n = 6/time point for water) were killed by decapitation 1, 6 and 24 hr after the last drinking episode. Brains were extracted and rapidly frozen in isopentane in dry ice. RNA was prepared from individual micropunch samples of the nucleus accumbens shell (ACB-sh) and central nucleus of the amygada (CeA); microarray analyses were conducted with Affymetrix Rat 230.2 chips. EtOH intakes were 1.5-2 g/kg/session. Because too few genes changed at the individual time points, an overall effect, comparing the water and EtOH groups, was determined. In the ACB-sh and CeA, there were 276 and 402 probe sets for named genes, respectively, that were different between the two groups. There were 1.5- to 3.5- fold more genes up-regulated than down-regulated in both regions, with most differences between 1.1- to 1.2-fold. Although there were several significant Biological Processes categories in common between the 2 regions (e.g., synaptic transmission, neurite development), there were few genes in common between the two regions that differed between the EtOH and water groups. Overall, the results suggest that chronic binge-like alcohol drinking by P rats produces changes in the expression of genes that could alter neuronal function by different mechanisms in the ACB-sh and CeA.
2009-12-31 | GSE15407 | GEO
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:The objective of this study was to test the hypothesis that innate differences in gene expression in the brain could contribute to the differences in alcohol drinking or response to alcohol between adult male inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU) and hippocampus (HIP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Significant differences between the two strains for each region were determined using Statistical Analysis of Microarrays (SAM). Using a false discovery rate threshold of 0.2, there were 46 genes with higher expression in iP rats and 61 genes with lower expression in the ACB, 111 genes with higher and 56 genes with lower expression in the AMYG, 61 genes with higher and 25 genes with lower expression in the FC, 39 genes with higher and 42 genes with lower expression in the CPU, and 35 genes with higher and 51 genes with lower expression in the HIP. In the AMYG, iP rats had higher expression of genes that are involved in neuronal growth and neurogenesis, e.g., brain derived neurotrophic factor, neuritin, etc. In contrast, in the ACB, iP rats had lower expression of genes involved in neurogenesis or cellular plasticity, e.g. cyclin E, vascular endothelial growth factor A. Many of the differences were in genes involved in intracellular signaling, cell membranes, extracellular matrix, and metabolism. These regional gene differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats. Keywords: alcohol, inbred, rat, gene expression, brain, nucleus accumbens, amygdala, frontal cortex, hippocampus, caudate-putamen
2007-07-28 | GSE4494 | GEO
Project description:The objective of this study was to test the hypothesis that innate differences in gene expression in the brain could; contribute to the differences in alcohol drinking or response to alcohol between adult male inbred alcohol-preferring (iP) and -non-preferring; (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU) and; hippocampus (HIP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Significant differences between the two strains for each region were determined using Statistical Analysis of Microarrays (SAM). Using a false discovery rate threshold of 0.2, there were 46 genes with higher expression in iP rats and 61 genes with lower expression in; the ACB, 111 genes with higher and 56 genes with lower expression in the AMYG, 61 genes with higher and 25 genes with lower expression in the FC,; 39 genes with higher and 42 genes with lower expression in the CPU, and 35 genes with higher and 51 genes with lower expression in the HIP. In the AMYG, iP rats had higher expression of genes that are involved in neuronal growth and neurogenesis, e.g., brain derived neurotrophic factor,; neuritin, etc. In contrast, in the ACB, iP rats had lower expression of genes involved in neurogenesis or cellular plasticity,; e.g. cyclin E, vascular endothelial growth factor A. Many of the differences were in genes involved in intracellular signaling,; cell membranes, extracellular matrix, and metabolism. These regional gene differences between the iP and iNP rat lines may contribute to; the divergent alcohol drinking phenotypes of these rats. Experiment Overall Design: Brain regions (accumbens, amygdala, frontal cortex, hippocampus, and striatum) from 6 biologic replicates of the selected inbred alcohol preferring and non-preferring lines iP5C and iNP1 were dissected and subjected to microarray analysis for comparison.
2008-11-22 | E-GEOD-4494 | biostudies-arrayexpress