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Genome-wide analysis of nucleus accumbens gene expression after ethanol consumption in rat

ABSTRACT: The study investigated ethanol-induced alterations in the transcriptome of adult male Wistar rats. The study was divided into two parts. Part 1: 10 animals were single housed during 8 weeks and exposed to 6% ethanol solution and water simultaneously or just water (24 hours/day, 7 days/week). Fluid intake and body weight were recorded twice weekly during 8 weeks. Animals were sacrificed immediately after the last consumption measurement and the nucleus accumbens were dissected and snap frozen until further processing. Part 2: 12 rats were single housed and exposed to continuous access to ethanol and water (24 hours/day, 7 days/week). After 4 weeks, animals were divided into 2 groups, equally balanced based on previous ethanol intake, and were given additional ethanol or water through a gavage tube daily during 3 weeks. This was followed by an additional 2 weeks of continuous ethanol access and then animals were immediately sacrificed and the nucleus accumbens were dissected and snap frozen until further processing. Next, the RNA was extracted from the cells using Qiagen RNeasy Lipid tissue mini kit and the RNA concentration and quality was measured using a BioAnalyzer. RNAseq was performed using standard Illumina protocols in collaboration with SciLifeLab, Stockholm, Sweden. No difference in gene expression was detected between any groups. Keywords: RNAseq, Gene expression profiles, Ethanol consumption, Rat.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE73627 | GEO | 2017/06/01

REPOSITORIES: GEO

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Project description:Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome. Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis. As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex. The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens

Project description:Here, we identify persistent and substantial variation in ethanol drinking behavior within an inbred mouse strain and utilize this model to identify gene networks influencing such non-genetic variation in ethanol intake. C57BL/6NCrl mice showed persistent inter-individual variation of ethanol intake in a two-bottle choice paradigm over a three week period, ranging from less than 1 g/kg to over 14 g/kg ethanol in an 18h interval. Whole genome microarray expression analysis in nucleus accumbens, prefrontal cortex and ventral tegmental area of individual animals identified gene expression patterns correlated with ethanol intake. Results included several gene networks previously implicated in ethanol behaviors, such as glutamate signaling, BDNF and genes involved in synaptic vesicle function. Additionally, genes functioning in epigenetic chromatin or DNA modifications such as acetylation and/or methylation also had expression patterns correlated with ethanol intake. Our results thus implicate specific brain regional gene networks, including chromatin modification factors, as potentially important mechanisms underlying individual variation in ethanol intake. Voluntary two-bottle choice drinking was performed as described previously (Khisti et al. 2006). Briefly, two bottles containing 10%(w/v) ethanol (Aaper Alcohol and Chemical Co. Shelbyville, KY) or tap water were placed into the home cage at the beginning of the dark cycle. Tube position was varied every two days (L, L, R, R). Drinking sessions lasted 18 hours/day followed by 6 hours access to water only. Mice had four consecutive drinking sessions followed by four days of abstinence repeated four times to give 16 total drinking sessions. Three brain regions were harvested 6 days after the last drinking session: prefrontal cortex (PFC), nucleus accumbens (NAc) and ventral tegmental area (VTA) as previously described (Kerns et al. 2005). Labeled cRNA from individual animals (n=19) was hybridized to a single microarray for each brain region (n=58 total microarrays).

Project description:To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages. Five-week-old C3H/HeN female mice (CLEA, Japan) were acclimated to the maintenance condition (25Â°C, 8:00-20:00 day / 20:00-8:00 night cycle and 35~40 % humidity), fed a CE-2 diet (CLEA, Japan), and given water ad libitum for one week. Each group of mice (n=4 for wild type mice analysis and n=3 for CAR decficient mice analysis) was fed Lieber's isocaloric diet (Oriental yeast, Japan) containing water, containing ethanol, containing ethanol and ellagic acid (Fluka Biochemika, Switzerland), or containing ethanol and trans-resveratrol (Sigma, USA) (Supplementary Table 1) for one week at 10:00 ad libitum. Then, the mice were fed each diet at 12 g / day for four weeks (Supplementary Fig. 1A). The approximate intake of each polyphenol was 50 mg / kg body weight / day. At 10:00 of the final day of the experimental period, the animals were anesthetized by diethyl ether, sacrificed by cervial fracture, and the heart blood, and the liver were collected.

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Genome-wide analysis of nucleus accumbens gene expression after ethanol consumption in rat

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