Alcohol-induced temporal transcriptome remodeling in the prefrontal cortex in a mouse model of alcohol dependence

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dc.contributor.advisorBergeson Susan E.
dc.creatorLodowski, Kerrie Hallen
dc.date.accessioned2015-04-28T16:27:40Zen
dc.date.accessioned2018-01-22T22:27:43Z
dc.date.available2015-04-28T16:27:40Zen
dc.date.available2018-01-22T22:27:43Z
dc.date.issued2006-08en
dc.descriptiontexten
dc.description.abstractAlcohol dependence (alcoholism) is a complex disease influenced by both environmental factors and genetic predisposition. Mouse models have been used to study many alcohol dependence-related traits and the genetics that underlie them. Two of the most commonly used mice in alcohol research are the C57BL/6J (B6) and DBA/2J (D2) inbred strains, which diverge on several alcohol-related traits including the development of acute physical dependence. Here we utilized the B6 and D2 mice as a genetic model of acute physical dependence, coupled with mRNA Differential Display (DD) and cDNA microarray analysis, to uncover the transcriptional response of the brain to an acute dose of alcohol as a function of time. About 150 genetically divergent and alcohol-responsive genes were identified between the whole brains of B6 and D2 mice using DD and were added as additional targets to the mouse microarrays. Microarray analysis of the prefrontal cortex of B6 and D2 mice revealed strain-specific, acute alcohol-responsive transcriptome remodeling manifested as temporal patterns of gene expression. Distinct expression patterns were identified for physiologically relevant alcohol-related consequences including intoxication, withdrawal and neuroadaptation. In silico characterization of the differentially expressed genes showed genotype dependent and independent transcriptional regulation and functional classification. In addition, categorization of differentially expressed genes by their cellular profiles revealed that some of the genes were known to be more highly expressed in either excitatory or inhibitory neuronal cell types. Our results indicate that the B6 and D2 prefrontal cortices have very different cellular and molecular responses to acute alcohol exposure. The specific roles that the genes identified in this study may play in mediating the divergent alcohol-related behavior between the strains warrant further study.en
dc.description.departmentCellular and Molecular Biologyen
dc.format.mediumelectronicen
dc.identifier.urihttp://hdl.handle.net/2152/29630en
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subjectAlcohol dependenceen
dc.subjectGenetic predispositionen
dc.subjectMice as genetic modelsen
dc.subjectGenetically divergenten
dc.subjectAlcohol-responsiveen
dc.subjectB6 and D2 miceen
dc.subjectTemporal transcriptome remodelingen
dc.subjectPrefrontal cortexen
dc.titleAlcohol-induced temporal transcriptome remodeling in the prefrontal cortex in a mouse model of alcohol dependenceen
dc.typeThesisen

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