Department of Psychology, University of Toronto Mississauga, Canada.
Behav Brain Res. 2011 Jan 1;216(1):66-76. doi: 10.1016/j.bbr.2010.07.017. Epub 2010 Jul 21.
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.
慢性酒精暴露会影响中枢神经系统，影响行为，并在包括人类在内的脊椎动物物种中引起神经适应性变化。由于酒精作用的复杂性，导致负责慢性酒精作用的分子机制尚未完全阐明。在这里，我们使用斑马鱼，一种酒精研究的新工具，来揭示大量对慢性酒精处理有反应的基因。我们使用全基因组 DNA 微阵列来证明对慢性酒精处理的差异基因表达，发现总共 1914 个基因的表达水平发生了至少 2 倍的显著变化（1127 个上调，787 个下调）。这些基因中约有三分之二以前没有已知的功能注释。微阵列分析的结果与通过定量实时 RT-PCR 分析的选定基因子集获得的结果非常吻合。对具有已知注释的差异表达基因的分析富集了多种分子功能。文献中报道的这些已知基因中只有一小部分与酒精有关。我们得出的结论是，斑马鱼是分析与脊椎动物中酒精作用相关基因的极好工具，这可能有助于发现和更好地理解酒精滥用的机制。
