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Fyn-dependent prefrontal cortex gene networks in acute ethanol sensitivity

ABSTRACT: Fyn kinase has been implicated in multiple behavioral responses to ethanol and in the regulation of myelin gene expression. Here we tested whether Fyn kinase modulated basal or ethanol-responsive expression of genes regulated by acute ethanol in brain regions of the mesolimbocortical dopamine pathway. Using expression profiling, we sought to define Fyn-dependent gene networks underlying ethanol behavioral traits; with emphasis on ethanol-induced loss of righting reflex (LORR) due to the reproducible association of Fyn kinase genotype with this behavioral phenotype (Miyakawa et al., 1997, Boehm et al., 2003, Yaka et al., 2003, Boehm et al., 2004b). Our expression profiling and bioinformatics results suggest multiple Fyn-related mechanisms, especially those affecting a network of myelin-related gene expression within the medial PFC, as contributing to the sedative-hypnotic properties of ethanol. Variation in the expression of these Fyn-dependent gene networks may be critical molecular endophenotypes affecting the behavioral level of response to acute ethanol, and subsequently, the long-term risk for alcohol use disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE49028 | GEO | 2014/08/31

SECONDARY ACCESSION(S): PRJNA212706

REPOSITORIES: GEO

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Fyn-dependent prefrontal cortex gene networks in acute ethanol sensitivity

Project description:Fyn kinase has been implicated in multiple behavioral responses to ethanol and in the regulation of myelin gene expression. Here we tested whether Fyn kinase modulated basal or ethanol-responsive expression of genes regulated by acute ethanol in brain regions of the mesolimbocortical dopamine pathway. Using expression profiling, we sought to define Fyn-dependent gene networks underlying ethanol behavioral traits; with emphasis on ethanol-induced loss of righting reflex (LORR) due to the reproducible association of Fyn kinase genotype with this behavioral phenotype (Miyakawa et al., 1997, Boehm et al., 2003, Yaka et al., 2003, Boehm et al., 2004b). Our expression profiling and bioinformatics results suggest multiple Fyn-related mechanisms, especially those affecting a network of myelin-related gene expression within the medial PFC, as contributing to the sedative-hypnotic properties of ethanol. Variation in the expression of these Fyn-dependent gene networks may be critical molecular endophenotypes affecting the behavioral level of response to acute ethanol, and subsequently, the long-term risk for alcohol use disorders. Adult male control (B6129SF2/J) and Fyn-kinase null (B6;129S7-Fyntm1Sor/J) mice were treated with saline or ethanol (3.0 g/kg x 4 hours) and brain regions harvested by microdissection for total RNA expression profiling by Affymetrix microarrays. Samples were randomly assigned to batch groups prior to total RNA extraction, cRNA synthesis and hybridization. Each microarray represents a pooling of 3 animals and 3 arrays were analyzed per treatment group for a total of 12 arrays per brain region. Statistical and bioinformatics analysis was used to identify Fyn-dependent effects on basal and ethanol-responsive gene expression, with a particular focus on myelin-related gene expression. This series of samples includes medial prefrontal cortex (PFC).

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