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首页> 外文期刊>BMC Neuroscience >Time-specific microRNA changes during spinal motoneuron degeneration in adult rats following unilateral brachial plexus root avulsion: ipsilateral vs. contralateral changes
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Time-specific microRNA changes during spinal motoneuron degeneration in adult rats following unilateral brachial plexus root avulsion: ipsilateral vs. contralateral changes

机译：成年大鼠单侧臂丛神经根撕脱后脊髓运动神经元变性期间的时间特异性microRNA变化：同侧与对侧变化

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Background Spinal root avulsion induces multiple pathophysiological events consisting of altered levels of specific genes and proteins related to inflammation, apoptosis, and oxidative stress, which collectively result in the death of the affected motoneurons. Recent studies have demonstrated that the gene changes involved in spinal cord injury can be regulated by microRNAs, which are a class of short non-coding RNA molecules that repress target mRNAs post-transcriptionally. With consideration for the time course of the avulsion-induced gene expression patterns within dying motoneurons, we employed microarray analysis to determine whether and how microRNAs are involved in the changes of gene expression induced by pathophysiological events in spinal cord motoneurons. Results The expression of a total of 3,361 miRNAs in the spinal cord of adult rats was identified. Unilateral root-avulsion resulted in significant alterations in miRNA expression. In the ipsilateral half compared to the contralateral half of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated, and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR-31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only miR-466c-3p presented a sustained decrease 3 and 14?days after the injury. More interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd day but were downregulated on the 14th day after injury. Some of these miRNAs target inflammatory-response genes in the early stage of injury, and others target neurotransmitter transport genes in the intermediate stages of injury. The altered miRNA expression pattern suggests that the MAPK and calcium signaling pathways are consistently involved in the injury response. Conclusions This analysis may facilitate the understanding of the time-specific altered expression of a large set of microRNAs in the spinal cord after brachial root avulsion.
机译：背景脊髓根部撕脱引起多种病理生理事件，包括与炎症，细胞凋亡和氧化应激相关的特定基因和蛋白质水平的改变，共同导致受影响的运动神经元死亡。最近的研究表明，与脊髓损伤有关的基因变化可以由microRNA调控，microRNA是一类短的非编码RNA分子，可在转录后抑制靶mRNA。考虑到垂死的运动神经元内撕脱引起的基因表达模式的时程，我们采用微阵列分析来确定microRNA是否以及如何参与由脊髓运动神经元的病理生理事件诱导的基因表达的变化。结果鉴定了成年大鼠脊髓中总共3,361个miRNA表达。单侧根撕脱导致miRNA表达的显着改变。与脊髓对侧一半相比，在同侧一半，损伤后第3天，上调了55个miRNA，下调了24个，在损伤后第14天，上调了36个miRNA，下调了23个。观察到miR-146b-5p和miR-31a-3p的上调以及miR-324-3p和miR-484的下调。包括miR-21-5p在内的11种miRNA表现出持续的增加;然而，仅miR-466c-3p在损伤后3天和14天持续下降。更有趣的是，包括miR-18a在内的4个miRNA在损伤后第3天被上调，而在损伤后第14天被下调。这些miRNA中的一些在损伤的早期靶向炎症反应基因，其他一些在损伤的中期靶向神经递质转运基因。改变的miRNA表达模式表明，MAPK和钙信号通路始终参与损伤反应。结论这项分析可能有助于理解臂根撕脱术后脊髓中大量microRNA的时间特异性改变。

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