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Chunk #33 — 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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Additional evidence for a role of miRNAs in the regulation of endocytotic recycling of neurotransmitter receptors is found in the work of the Li group, who found that miR-140* is upregulated by nicotine treatment and directly binds to dynamin (Dnm1) mRNA to inhibit its expression (Huang and Li, 2008). Dynamin-1 is involved in scission of clathrin-coated vesicles and it is essential for endocytotic synaptic vesicle recycling only during the application of a strong or sustained stimulus when exocytosis of neurotransmitter-filled vesicles is extreme and rapid retrieval of vesicles is required to maintain the synaptic vesicle pool (Ferguson et al., 2007; Etheridge et al., 2009). Proteomic studies of synaptosomal fractions from superior frontal gyrus and occipital cortex of postmortem human brains identified dynamin-1 protein as differentially regulated between alcoholics and controls (decreased expression in alcoholics) and provided evidence for differential alteration of multiple protein isoforms in a brain region-specific manner (Etheridge et al., 2009). Furthermore, our group has demonstrated that dynamin-1 establishes a strong physical interaction with the large conductance voltage- and calcium-activated potassium channel (BKCa), another major player in alcohol