In addition to innate immune responses, the differentially expressed miRNAs identified in human frontal cortex from alcoholics coordinate many other biological processes. For example, miR-7 and miR-153 regulate α-synuclein, which plays a role in dopaminergic transmission, activity-dependent maintenance of SNARE complex levels in pre-synaptic terminals (Burgoyne and Morgan, 2011; Burre et al., 2010), and neurodegenerative disorders (Doxakis, 2010). Furthermore, there is a large body of evidence linking α-synuclein accumulation to alcohol dependence in humans and rodents (Bonsch et al., 2005; Taraskina et al., 2008). miR-9 acts as a posttranscriptional regulator of splice variation and neuroadaptations that underlie alcohol tolerance (Farris et al., 2015a; Pietrzykowski et al., 2008). Noteworthy targets of miR-9 include the BK potassium channel KCNMA1 and GAD1 which are involved in neuronal excitability and alcohol behavioral phenotypes (Bettinger and Davies, 2014). Several members of the let-7 family have been reported to regulate mu-opioid, β2-adrenergic, and dopamine D3 receptors (Chandrasekar and Dreyer, 2009; Pillai et al., 2005). Moreover, miR-101 has been implicated in the modulation of GABAergic transmission in response to alcohol consumption (Saba et al., 2012). Taken together, these studies suggest that alcohol-responsive miRNAs may regulate a variety of neurotransmitter-regulated pathways in the frontal cortex of human alcoholics.
