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Chunk #32 — Human Alcohol-Responsive Mirnas, Neurotransmitter Signaling, and Synaptic Plasticity

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Understanding Alcoholism Through microRNA Signatures in Brains of Human Alcoholics.
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On the other hand, support for an involvement of miR-101 (another miRNA upregulated in the PFC of human alcoholics) in the modulation of GABAergic transmission in response to alcohol consumption can be found in a recent study conducted by the Tabakoff group (Saba et al., 2011). After analyzing gene expression profiles induced by alcohol-drinking in panels of recombinant and isogenic inbred mice, Saba and colleagues found that guanine nucleotide binding protein beta 1 subunit (Gnb1) was the only transcript that changed expression in all groups of high and low alcohol-drinking mice and, in addition, localized within a quantitative trait loci for alcohol consumption. Gnb1 expression level was inversely related to the level of alcohol intake. Based on differential detection of Gnb1 transcript variants, protein levels, and 3′ UTR sequence analysis, the authors suggested that miR-101 could be regulating the amount of Gβ1 protein. Gβ1 protein can initiate a cascade of intracellular signaling events leading to the internalization of GABAA and other receptors (Saba et al., 2011). Although subsequent studies investigating the direct interaction between miR-101 and the Gnb1 transcripts are necessary for validation, we are enthusiastic about the emergence of seemingly interconnected patterns spanning multiple animal species.