Chronic alcohol exposure induced gene expression changes in the zebrafish brain

Chronic alcohol exposure affects the central nervous system, influences behavior, and induces neuroadaptive changes in vertebrate species including our own. The molecular mechanisms responsible for chronic alcohol effects have not been fully elucidated due to the complexity of alcohol's actions. Here we use zebrafish, a novel tool in alcohol research, to reveal a large number of genes that respond to chronic alcohol treatment. We demonstrate differential gene expression in response to chronic alcohol treatment using full genome DNA microarrays and find a total of 1914 genes to show a minimum of 2-fold and significant expression level change (1127 were up- and 787 were down-regulated). Approximately two-thirds of these genes had no known previous functional annotation. The results of the microarray analyses correlated well with those obtained on a selected subset of genes analyzed by quantitative real-time RT-PCR. Analyses of the differentially expressed genes with known annotations were enriched for a variety of molecular functions. Only a fraction of these known genes has been reported in the literature to be alcohol related. We conclude that the zebrafish is an excellent tool for the analysis of genes associated with alcohol's actions in vertebrates, one which may facilitate the discovery and better understanding of the mechanisms of alcohol abuse.

Research highlights▶This study is a DNA microarray analysis of gene expression changes induced by chronic alcohol (EtOH) exposure in zebrafish. ▶The study focuses on mRNA expression changes in the brain of zebrafish. ▶It identifies close to 2000 differentially expressed genes some of which have been shown to be involved in alcohol related mechanisms as well as others whose function in alcohol induced CNS processes has not been shown before. ▶The study is the most comprehensive microarray analysis in zebrafish thus far and represents a starting point for numerous follow-up investigations including behavioral characterization of alcohol effects as well as functional characterization of genes in alcohol related responses.