Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, USA.
Neurosci Lett. 2013 Oct 11;553:153-8. doi: 10.1016/j.neulet.2013.08.001. Epub 2013 Aug 21.
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 we analyzed the possible role of miRs in the neurodegenerative process in a spontaneous autosomal recessive rat model for neurodegeneration developed in our laboratory. To investigate the role of miRs in the etiology of PD, we conducted miR expression profiling using microarrays. We found 20 miRs that are deregulated in affected rats and many of these are implicated in neurodegenerative disease, including PD. In this study we 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. We found a significant increase in miR-132 in affected rats by microarray and the result was confirmed by qPCR. Next we 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, we 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.
微小 RNA（miRs）是内源性的小 RNA，通过介导 mRNA 降解或转录抑制来在转录后水平调节基因表达。miRs 参与了许多神经退行性疾病的发病机制，包括帕金森病（PD）。在本研究中，我们分析了 miRs 在我们实验室开发的自发性常染色体隐性遗传神经退行性疾病大鼠模型的神经退行性过程中的潜在作用。为了研究 miRs 在 PD 发病机制中的作用，我们使用微阵列进行了 miR 表达谱分析。我们发现 20 个在受影响的大鼠中失调的 miRs，其中许多与神经退行性疾病有关，包括 PD。在本研究中，我们特别关注 miR-132 的表达，据报道，miR-132 在神经元中高度表达，并可能在神经退行性疾病中发挥作用。我们通过微阵列发现受影响的大鼠中 miR-132 的表达显著增加，qPCR 结果也证实了这一点。接下来，我们分析了 miR-132 的一个已知下游靶标，核受体相关 1 蛋白（Nurr1），它在中脑多巴胺能神经元的神经发生中至关重要。Western blot 分析和免疫组织化学显示，中脑神经元中的 Nurr1 蛋白表达显著降低。最后，我们发现血清和脑组织中脑源性神经营养因子（BDNF）的水平均显著降低，BDNF 已知是 Nurr1 的直接靶标。总之，我们的研究结果表明，miR-132 可以调节 Nurr1 水平，并可能影响中脑多巴胺能神经元的发育和功能。
