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Publication Abstract Display
Type: Poster
Title: MicroRNA-9 is increased in CNS HIV-infection and methamphetamine exposure.
Authors: Tatro ET, Hefler S, Shumaker S, Yang M, Soontornyiomkij B, Achim C
Date: 05-29-2012
Abstract:MicroRNAs (miR) regulate phenotype and function of neurons by binding to miR-response elements (MRE) in the 3′ untranslated regions (3′UTR) of various messenger RNAs to inhibit translation. MiR expression can be induced or inhibited by environmental factors like drug exposure and viral infection, leading to changes in cellular physiology. We hypothesized that the combined effects of methamphetamine (Meth) and human immunodeficiency virus (HIV)- infection in the brain will induce changes in miR expression, and have downstream regulatory consequences in neurons. We first used a PCR-based array to screen for differential expression of 380 miRs in the frontal cortex of HIV-positive Meth abusers and matched controls using frozen autopsy tissues. The screening results showed significantly increased expression of the neuronspecific miR-9. In vitro, we used SH-SY5Y cells, an experimental system for dopaminergic studies, to determine miR expression by quantitative PCR after exposure to Meth in the presence or absence of conditioned media from HIV-infected macrophages. Again, we found that miR-9 was three-fold increased compared to controls. We also examined the inwardly rectifying potassium channel, KCNMA1, which has alternative splice variants that contain an MRE to miR-9. We employed the Rapid Extension of cDNA Ends technique to identify alternate 3′UTRs of KCNMA1 both in vitro and in the autopsy specimens. We are currently testing whether differential splice variant expression of KCNMA1 operates via the increased miR-9, by pretreating the neurons with anti-miR-9 locked nucleic acid. Our preliminary results suggest that HIV and Meth -induced elevated miR-9 leads to suppression of MRE-containing splice variants of the inwardly rectifying potassium channel, KCNMA1, which may affect neurotransmitter release in dopaminergic neurons. MiR-9 may be a therapeutic target for Meth abuse in HIVpositive individuals.

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