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

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

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.

Keywords: Axotomy; Mice; Motoneurons; c-Jun; siRNA.

MeSH terms

  • Accessory Nerve Injuries / therapy*
  • Animals
  • Brachial Plexus / injuries
  • Brachial Plexus / metabolism
  • Gene Silencing
  • JNK Mitogen-Activated Protein Kinases / genetics*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Motor Neurons / metabolism*
  • Motor Neurons / physiology
  • RNAi Therapeutics / methods*
  • Spinal Cord Ventral Horn / cytology
  • Spinal Cord Ventral Horn / metabolism
  • Spinal Cord Ventral Horn / physiology

Substances

  • JNK Mitogen-Activated Protein Kinases