Dicer-microRNA pathway is critical for peripheral nerve regeneration and functional recovery in vivo and regenerative axonogenesis in vitro.
Dicer-microRNA pathway is critical for peripheral nerve regeneration and functional recovery in vivo and regenerative axonogenesis in vitro.
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DOI：
10.1016/j.expneurol.2011.11.041
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发表时间：
2012-01
影响因子：
5.3
通讯作者：
Murashov, Alexander K.
中科院分区：
文献类型：
--
作者：
Wu, Di;Raafat, Abdalla;Pak, Elena;Clemens, Stefan;Murashov, Alexander K.
中枢和外周轴突都含有关键的microRNA（miRNA）蛋白。虽然最近的观察表明，miRNA的生物合成机制响应于周围神经损伤的损伤调节模式，这种现象的生理意义仍有待阐明。在目前的论文中，我们假设Dicer的缺失会破坏Dicer依赖性miRNA的产生，并对再生轴突生长产生负面影响。利用他莫昔芬诱导的CAG-CreERt：Dicerfl/fl敲除（Dicer KO），我们研究了Dicer缺失对坐骨神经再生的体内结果和再生轴突生长的体外结果。在这里，我们表明，坐骨神经功能指数，一个指标的功能恢复，是显着较低的Dicer基因敲除小鼠相比，野生型动物。恢复的机械灵敏度记录在冯弗雷测试也明显受损的切丁突变体。此外，Dicer基因的缺失还阻碍了神经传导速度和诱发复合动作电位幅度的恢复。在组织学上，Dicer KO小鼠的再生神经纤维总数和平均轴突面积均明显较小。此外，Dicer缺陷的神经元未能再生轴突在分离的背根神经节（DRG）的文化。总之，我们的结果表明，敲除Dicer明显阻碍再生轴突生长以及解剖学，生理学和功能恢复。我们的数据表明，完整的Dicer依赖性miRNA通路是周围神经损伤后成功再生的关键。
Both central and peripheral axons contain pivotal microRNA (miRNA) proteins. While recent observation demonstrated that miRNA biosynthetic machinery responds to peripheral nerve lesion in an injury-regulated pattern, the physiological significance of this phenomenon remains to be elucidated. In the current paper we hypothesized that deletion of Dicer would disrupt production of Dicer-dependent miRNAs and would negatively impact regenerative axon growth. Taking advantage of tamoxifen-inducible CAG-CreERt:Dicerfl/fl knockout (Dicer KO), we investigated the results of Dicer deletion on sciatic nerve regeneration in vivo and regenerative axon growth in vitro. Here we show that the sciatic functional index, an indicator of functional recovery, was significantly lower in Dicer KO mice in comparison to wild-type animals. Restoration of mechanical sensitivity recorded in the von Frey test was also markedly impaired in Dicer mutants. Further, Dicer deletion impeded the recovery of nerve conduction velocity and amplitude of evoked compound action potentials in vitro. Histologically, both total number of regenerating nerve fibers and mean axonal area were notably smaller in the Dicer KO mice. In addition, Dicer-deficient neurons failed to regenerate axons in dissociated dorsal root ganglia (DRG) cultures. Taken together, our results demonstrate that knockout of Dicer clearly impedes regenerative axon growth as well as anatomical, physiological and functional recovery. Our data suggest that the intact Dicer-dependent miRNA pathway is critical for the successful peripheral nerve regeneration after injury.
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影响因子：
2.5
作者：
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