MicroRNAs (miRNA) are a class of non coding RNAs which modulate gene expression by binding to complementary sequence of target mRNA. Recently it has been attributed a role of miRNAs in neuroplasticity, learning and drug addiction. To investigate if cannabinoids induce long term neuroadaptative modifications in brain reward related areas and the role of miRNA in these modifications, we have performed a genome-wide analysis on 736 mature miRNAs in rats self-administering WIN 55,212-2 i.v. (SA). At the end of experiment, rats were sacrificed and brains removed for the extraction of miRNA from striatum, prefrontal cortex and nucleus accumbens (shell and core) by RealTime-PCR. Analysis revealed that WIN 55,212-2 SA was associated to up-or down regulation of different miRNAs for each brain regions. The number of regulated miRNAs was maximal in the CPu (11 up- and 99 down-regulated), in the shell (40 up- and 55 down-), and in the core (13 up and 83 down-) and to a lesser extent in the prefrontal cortex (26 up- and 27 down-). We also studied miRNAs target genes and performed the expression profiling analysis by using specific RealTime primers. Disregulated target genes were Drd3 (DAD3receptors), Bdnf, Mecp2 and Nos1. These results support the existing evidence that some miRNAs are key regulators of the reward circuits and may be implicated in long term neuroadaptative modifications induced by WIN 55,212-2.
Changes in miRNAs in WIN55,212-2 self-administration
VALENTINI, VALENTINA;SERRA, GIAN PIETRO;LECCA, DANIELE;
2014-01-01
Abstract
MicroRNAs (miRNA) are a class of non coding RNAs which modulate gene expression by binding to complementary sequence of target mRNA. Recently it has been attributed a role of miRNAs in neuroplasticity, learning and drug addiction. To investigate if cannabinoids induce long term neuroadaptative modifications in brain reward related areas and the role of miRNA in these modifications, we have performed a genome-wide analysis on 736 mature miRNAs in rats self-administering WIN 55,212-2 i.v. (SA). At the end of experiment, rats were sacrificed and brains removed for the extraction of miRNA from striatum, prefrontal cortex and nucleus accumbens (shell and core) by RealTime-PCR. Analysis revealed that WIN 55,212-2 SA was associated to up-or down regulation of different miRNAs for each brain regions. The number of regulated miRNAs was maximal in the CPu (11 up- and 99 down-regulated), in the shell (40 up- and 55 down-), and in the core (13 up and 83 down-) and to a lesser extent in the prefrontal cortex (26 up- and 27 down-). We also studied miRNAs target genes and performed the expression profiling analysis by using specific RealTime primers. Disregulated target genes were Drd3 (DAD3receptors), Bdnf, Mecp2 and Nos1. These results support the existing evidence that some miRNAs are key regulators of the reward circuits and may be implicated in long term neuroadaptative modifications induced by WIN 55,212-2.
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