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.
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.
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.
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.
Project description:Major depressive disorder (MDD) is considered as a neural circuit-based polygene syndrome that is mainly triggered by genetic susceptibility and stress factors. The present study employed the Wistar Kyoto (WKY) rat as an animal model with endogenous depression to further investigate the molecular basis of its genetic susceptibility to depression by performing quantitative protemoics analyses of the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and hippocampus (Hip), respectively.
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
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.
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.
Project description:The objective of this study was to determine common innate differences in gene expression in the Central Nucleus of the Amygdala (CeA) 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.