Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death after root avulsion in adult rats

• Spinal motoneuons express c-jun after avulsion injury.
• siRNA can be up-taken by injured motor neurons when applied intrathecally.
• siRNA not only inhibited the expression of both c-jun mRNA and protein but also augmented avulsed motoneuron death.
• Expression of c-jun plays a pivotal role for the survival of the injured spinal motoneurons.

The immediate-early gene, c-jun, is expressed in spinal motoneurons after spinal root avulsion. The expression of c-jun was suggested to be necessary for motoneuron survival and regeneration after avulsion. In the present study, a small interfering RNA (siRNA) was delivered intrathecally to the injured spinal segments immediately after root avulsion in rats to knock down expression of the c-jun gene in injured spinal motoneurons so as to explore the role of c-jun in the motoneurons in vivo. Our results showed that the siRNA not only inhibited the expression of both c-jun mRNA and protein but also augmented the death of injured motoneurons at day 14 post-injury. These findings indicated that induction of c-jun gene expression plays a pivotal role in the survival of injured motoneurons. Meanwhile, these results suggest that siRNAs applied intrathecally can effectively mediate the expression of the c-jun gene in injured motoneurons.

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