Estrogen-dependent up-regulation of Adcyap1r1 expression in nucleus accumbens is associated with genetic predisposition of sex-specific QTL for alcohol consumption on rat chromosome 4
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE112399 | GEO | 2018/09/27
REPOSITORIES: GEO
Similar Datasets
Project description:The objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. Comparison of Differences in Gene Expression in the Nucleus Accumbens Shell of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption.
2012-07-31 | E-GEOD-31705 | biostudies-arrayexpress
Project description:The objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats.
2012-08-01 | GSE31705 | GEO
Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This is analysis of 18 RNA samples, including 9 technical replicates. Two strains of rats selected for extreme levels of ethanol preference (low preferring WLP and high preferring WHP) were compared. Three brain areas (nucleus accumbens, prefrontal medial cortex and hippocampus) were studied. For each brain area, 6 RNA samples (including 3 technical replicates) were analyzed. Each RNA sample consist of of equal amounts of total RNA from 3 male rats. Comparisons: Nucleus accumbens of WHP vs. Nucleus accumbens of WLP; Prefrontal medial cortex of WHP vs. Prefrontal medial cortex of WLP; Hippocampus of WHP vs. Hippocampus of WLP. 3 biological replicates in each comparison.
2015-01-17 | E-GEOD-65064 | biostudies-arrayexpress
Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This study was supported through funding from the following grants: Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants “Iuventus Plus” (IP2011 030371) and N N519 657940.
2015-01-17 | GSE65064 | GEO
Project description:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naïve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included âÂÂnegative regulation of protein kinase activityâÂÂ, âÂÂanti-apoptosisâÂÂ, and âÂÂregulation of G-protein-coupled receptor protein signaling pathwayâÂÂ. Ingenuityî analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Experiment Overall Design: 10 samples each of control, continuous ethanol and limited access ethanol
2009-09-25 | E-GEOD-13524 | 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. 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: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. Differences in gene expression in brain nucleus accumbens shell (Acb-sh) 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-49041 | 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:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naïve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included ‘negative regulation of protein kinase activity’, ‘anti-apoptosis’, and ‘regulation of G-protein-coupled receptor protein signaling pathway’. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Keywords: comparison of gene expression profiles for treated vs. control
2009-09-01 | GSE13524 | 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)
2009-12-31 | GSE15415 | GEO