gene expression often occur over a narrow range of only 20-30% (Hobert, 2007; Peter, 2010). In our study we also found that the alcohol-induced up-regulation of miRNAs was constrained in a similar range, with only a few miRNAs varying levels in more than 30%. We speculate that negative feedback loops between Dicer and specific miRNAs could serve as a general mechanism for tight, global regulation of miRNA levels. The importance of feedback loops in homeostasis and cellular differentiation programs has been highlighted (Alon, 2007; Martinez et al., 2008) and the role of Dicer as a stress response component suggested (Wiesen and Tomasi, 2009). We reason that remodeling of cellular homeostasis could be taking place in the brain of chronic alcohol abusers as an adaptive mechanism, particularly in this specific cohort of alcoholic individuals, who had spent most of their adult lives consuming high quantities of ethanol without developing complicated alcohol-related disorders an indication of benign adaptation to the increased concentrations of alcohol in brain and other tissues.
