Genetic approaches to alcohol addiction: gene expression studies and recent candidates from Drosophila

Abstract

Ethanol intake causes gene expression changes resulting in cellular and molecular adaptations that could be associated with a predisposition to alcohol dependence. Recently, several research groups have used high-throughput gene expression profiling to search for alcohol-responsive genes in Drosophila melanogaster. Comparison of data from these studies highlights the functional similarities in their results despite differences in their experimental approach and selection cases. Notably, alcohol-responsive gene sets associated with stress response, olfaction, metabolism, proteases, transcriptional regulation, regulation of signal transduction, nucleic acid binding and cytoskeletal organisation were markedly common to these studies. These data support the view that changes in gene expression in alcoholics are associated with widespread cellular functions.

Transcriptional basis of the acclimation to high environmental temperature at the olfactory receptor organs of Drosophila melanogaster

“…Due to the social impact of alcoholism, several microarray studies have focused on understanding the molecular changes that occur after exposure to ethanol using various model organisms [13]. Thus, it is known that in D. melanogaster , exposure to ethanol causes a decrease in the expression of genes affecting olfaction, among other changes [14-17].…”

Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain

“…In the nematode, ethanol exposure rapidly induced a cellular stress response (heat shock protein genes) [16]. Gene profiling in the fruit fly also identified ethanol-responsive gene sets associated with stress response, along with olfaction, metabolism, transcription and signal transduction [17]. The present review focuses on whole-genome expression profiling in rodent genetic models of differential ethanol sensitivity or consumption, in rodents acutely or chronically exposed to ethanol and in human alcoholics.…”

Genetics and genomics of alcohol sensitivity

“…Using a similar approach we compiled findings from several transcriptional profiling studies that have identified differentially expressed genes from alcohol-related studies on D. melanogaster (Morozova et al 2006, 2007, 2009, 2011; Urizar et al 2007; Awofala 2010; Kong et al 2010); from alcohol-related expression studies done on mice (Xu et al 2001; Daniels and Buck 2002; Tabakoff et al 2003; Hitzemann et al 2004; Saito et al 2004; Treadwell and Singh 2004; Kerns et al 2005; MacLaren et al 2006; Mulligan et al 2006, 2011; Saba et al 2006; Wang et al 2007; Denmark and Buck 2008; Wolstenholme et al 2011), and transcriptional profiling data on rats (Rimondini et al 2002; Edenberg et al 2005; Worst et al 2005; Carr et al 2007; Kimpel et al 2007; Rodd et al 2008), and identified human orthologs. In addition, we analyzed six published transcriptional profiling data sets performed on different areas of postmortem human brains and also included candidate genes for alcohol-related phenotypes from the HuGE Navigator database (Lewohl et al 2000; Mayfield et al 2002; Sokolov et al 2003; Iwamoto et al 2004; Flatscher-Bader et al 2005; Liu et al 2006a; Guo et al 2009).…”