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Chunk #48 — Discussion — miR-9 can serve as a master-switch for alcohol effects in the CNS

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Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol.
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The miR-9 dependent downregulation of target mRNA and reorganization of its splice variants may represent a general mechanism of neuronal adaptation to alcohol. We determined that miR-9 affects at least ten additional targets besides BK with documented roles in alcohol actions in the CNS (Table 1, Supplementary Materials), some of which can undergo alternative splicing (SYNJ1, DRD2). Moreover, we observed that the expression of these targets is regulated by brief alcohol exposure. These additional downstream targets of miR-9 are involved in major aspects of neuronal physiology (for details see Supplementary Materials) including excitability, regulation of gene expression, metabolism of lipids and function of presynaptic terminals.