Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Illumina microarray analysis of brain regions following acute exposure to bilirubin or LPS

ABSTRACT: We developed a novel mouse model of acute bilirubin toxicity. 450mg/kg bilirubin was administered IP to mice, which exhibited transient hearing deficits and ataxia at 4 hours, and recovered by 24 hours. This toxicity is consistent with the human symptoms of bilirubin toxicity. To investigate the molecular mechanisms of bilirubin toxicity we carried out whole genome gene expression analysis on gross brain regions (cortex, cerebellum and brainstem) and specific parts of the auditory pathway (MNTB and CN) at 2 hours, 4 hours and 24 hours post injection. We detected several transcriptional markers of neuroinflammation, and so developed a second set of data for the same brain regions and time points following injection of a well characterized neuroinflammatory agent; LPS (5mg/kg).

ORGANISM(S): Mus musculus

SUBMITTER: Joshua Smalley

PROVIDER: E-MTAB-7102 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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).

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Illumina microarray analysis of brain regions following acute exposure to bilirubin or LPS

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