MicroRNAs (miRs) are endogenous small RNAs that regulate gene expression at the post-transcriptional level by mediating mRNA degradation or transcriptional inhibition. MiRs were implicated in the pathogenesis of numerous neurodegenerative diseases, including Parkinson’s disease (PD). In this study researchers from Texas A&M University analyzed the possible role of miRs in the neurodegenerative process in a spontaneous autosomal recessive rat model for neurodegeneration developed in their laboratory. To investigate the role of miRs in the etiology of PD, they conducted miR expression profiling using microarrays. The researchers found 20 miRs that are deregulated in affected rats and many of these are implicated in neurodegenerative disease, including PD. In this study they were particularly interested in the expression of miR-132, a miR that has been reported to be highly expressed in neurons, and to have a potential role in neurodegenerative diseases. They found a significant increase in miR-132 in affected rats by microarray and the result was confirmed by qPCR. Next they analyzed one of the known downstream targets of miR-132, nuclear receptor related 1 protein (Nurr1), which is essential in neurogenesis of midbrain dopaminergic neurons. Western blot analysis and immunohistochemistry revealed a significant decrease in Nurr1 protein expression in the mesencephalic neurons. Finally, the researchers found a significant decrease in both serum and mesencephalon brain tissue of brain-derived neurotrophic factor (BDNF), which is known to be a direct target of Nurr1. Taken together, our findings suggest that miR-132 can regulate Nurr1 levels and might influence the development and function of midbrain dopaminergic neurons.
(A) Heatmap of miR expression profile in the brain of BD-IV affected (n = 3) and control (n = 3) rats at 25 dpn. The green color denotes down-regulated expression and the red color denotes up-regulated expression level of miRs. (B) miR-132 expression levels. MiR-132 levels were determined in affected (n = 3) and control (n = 3) BD-IV rats by qPCR. Data are presented as the means ± standard deviation from three independent experiments (*P < 0.05)
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Reference
Lungu G, Stoica G, Ambrus A. (2013) MicroRNA profiling and the role of microRNA-132 in neurodegeneration using a rat model. Neuroscience Letters 153-158 [abstract]