Title:Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain
VOLUME: 1 ISSUE: 4
Author(s):Candice Contet
Affiliation:The Scripps Research Institute, Committee on the Neurobiology of Addictive Disorders, 10550 North Torrey Pines Road, SP-102, La Jolla, CA, USA.
Keywords:Ethanol, alcohol, gene expression, transcriptome, profiling, microarray, RNA-seq, brain, Transcriptomics, microRNAs, Gene Ontology, DNMT1, DNA hypomethylation, nucleotides
Abstract:Sensitivity to ethanol intoxication, propensity to drink ethanol and vulnerability to develop alcoholism are all
influenced by genetic factors. Conversely, exposure to ethanol or subsequent withdrawal produce gene expression
changes, which, in combination with environmental variables, may participate in the emergence of compulsive drinking
and relapse. The present review offers an integrated perspective on brain gene expression profiling in rodent models of
predisposition to differential ethanol sensitivity or consumption, in rats and mice subjected to acute or chronic ethanol
exposure, as well as in human alcoholics. The functional categories over-represented among differentially expressed genes
suggest that the transcriptional effects of chronic ethanol consumption contribute to the neuroplasticity and neurotoxicity
characteristic of alcoholism. Importantly, ethanol produces distinct transcriptional changes within the different brain
regions involved in intoxication, reinforcement and addiction. Special emphasis is put on recent profiling studies that have
provided some insights into the molecular mechanisms potentially mediating genome-wide regulation of gene expression
by ethanol. In particular, current evidence for a role of transcription factors, chromatin remodeling and microRNAs in
coordinating the expression of large sets of genes in animals predisposed to excessive ethanol drinking or exposed to
protracted abstinence, as well as in human alcoholics, is presented. Finally, studies that have compared ethanol with other
drugs of abuse have highlighted common gene expression patterns that may play a central role in drug addiction. The
availability of novel technologies and a focus on mechanistic approaches are shaping the future of ethanol transcriptomics.
