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小干扰 RNA(siRNA)预注射促进 c-Jun 基因沉默并降低成年小鼠轴突切断损伤脊髓运动神经元的存活率。

Pre-Injection of Small Interfering RNA (siRNA) Promotes c-Jun Gene Silencing and Decreases the Survival Rate of Axotomy-Injured Spinal Motoneurons in Adult Mice.

机构信息

Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.

Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, No.52 Mei Hua East Road, Zhuhai, 519000, Guangdong Province, People's Republic of China.

出版信息

J Mol Neurosci. 2018 Jul;65(3):400-410. doi: 10.1007/s12031-018-1098-y. Epub 2018 Jul 10.

DOI:10.1007/s12031-018-1098-y
PMID:29992498
Abstract

Brachial plexus injury is a common clinical peripheral nerve trauma. A series of genes in motoneurons were activated in the corresponding segments of the spinal cord after brachial plexus roots axotomy. The spatial and temporal expression of these genes directly affects the speed of motoneuron axon regeneration and precise target organ reinnervation. In a previous study, we observed the overexpression of c-Jun in motoneurons of the spinal cord ventral horn after brachial plexus injury in rats. However, the relevance of c-Jun expression with respect to the fate of axotomy-induced branchial plexus injury in adult mice remains unknown. In the present study, we explored the function of c-Jun in motoneuron recovery after axotomy. We pre-injected small interfering RNA (siRNA) to knockdown c-Jun expression in mice and examined the effects of the overexpression of c-Jun in motoneurons after the axotomy of the brachial plexus in vivo. Axotomy induced c-Jun overexpression in the ventral horn motoneurons of adult mice from 3 to 14 days after injury. In addition, the pre-injection of siRNA transiently inhibited c-Jun expression and decreased the survival rate of axotomy-injured motoneurons. These findings indicate that the axotomy-induced overexpression of c-Jun plays an important role in the survival of ventral horn motoneurons in adult mice. In addition, the pre-injection of c-Jun siRNA through the brachial plexus stem effectively adjusts c-Jun gene expression at the ipsilateral side.

摘要

臂丛神经损伤是一种常见的临床周围神经创伤。在臂丛神经根切断后,脊髓相应节段的运动神经元中一系列基因被激活。这些基因的时空表达直接影响运动神经元轴突再生的速度和精确的靶器官再支配。在之前的研究中,我们观察到大鼠臂丛损伤后脊髓前角运动神经元中 c-Jun 的过表达。然而,c-Jun 表达与成年小鼠臂丛损伤后轴突切断的命运之间的相关性尚不清楚。在本研究中,我们探讨了 c-Jun 在运动神经元轴突切断后恢复中的作用。我们预先注射小干扰 RNA(siRNA)以敲低小鼠中 c-Jun 的表达,并在体内观察臂丛神经轴突切断后 c-Jun 在运动神经元中的过表达对其的影响。轴突切断后,成年小鼠脊髓前角运动神经元中的 c-Jun 在损伤后 3 至 14 天过度表达。此外,siRNA 的预先注射可短暂抑制 c-Jun 的表达,并降低轴突损伤运动神经元的存活率。这些发现表明,轴突切断诱导的 c-Jun 过表达在成年小鼠脊髓前角运动神经元的存活中发挥重要作用。此外,通过臂丛神经干预先注射 c-Jun siRNA 可有效调节同侧的 c-Jun 基因表达。

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Erythropoietin Attenuates the Apoptosis of Adult Neurons After Brachial Plexus Root Avulsion by Downregulating JNK Phosphorylation and c-Jun Expression and Inhibiting c-PARP Cleavage.
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Exp Biol Med (Maywood). 2019 Oct;244(13):1096-1110. doi: 10.1177/1535370219871868. Epub 2019 Aug 28.
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