Cell death-related genes were among the functionally enriched transcripts being targeted by miRNAs in our studies in PFC of human alcoholics (Liu et al., 2006b; Lewohl et al., 2011). A study from the Bakalkin group, also using postmortem PFC of human alcoholics, provides additional support for our findings. These authors found that dysregulation of the cell death machinery by inhibition of the intrinsic apoptotic pathway “may reflect molecular adaptations that counteract alcohol neurotoxicity in cells that survive after many years of alcohol exposure and withdrawal” (Johansson et al., 2008). Although the Yadav group found opposite miRNA-mediated effects inducing neuronal death in cell cultures treated with ethanol for relatively short periods of time (3–72 h), their results do not contradict the neuroadaptive phenomenon we and others observe in chronic alcoholics, but seemingly describe initial effects of acute alcohol exposure as previously documented in animal models (Heaton et al., 1999; Rajgopal et al., 2003; Nowoslawski et al., 2005). Collectively, these findings support the notion that miRNA-mediated neuroadaptations may develop after an initial, also miRNA-mediated, activation of cell death pathways that occurs during the early stages of alcohol abuse.
