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Updated: May 13, 2026
In Vivo SiRNA Transfection and Gene Knockdown in Spinal Cord via Rapid Noninvasive Lumbar Intrathecal Injections in Mice
Published on: March 22, 2014
Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death
1Department of Anatomy, Zhong Shan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Abstract:
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.
Insights
The immediate-early gene c-jun is crucial for spinal motoneuron survival following injury. Inhibiting c-jun with small interfering RNA (siRNA) worsened motoneuron death, highlighting its protective role.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Immediate-early gene c-jun is expressed in spinal motoneurons post-spinal root avulsion.
- c-jun expression is hypothesized to be vital for motoneuron survival and regeneration after injury.
Purpose of the Study:
- To investigate the in vivo role of c-jun in injured spinal motoneurons.
- To determine if c-jun gene knockdown affects motoneuron survival after spinal root avulsion.
Main Methods:
- Small interfering RNA (siRNA) targeting c-jun was administered intrathecally to rats immediately after spinal root avulsion.
- c-jun mRNA and protein levels were assessed post-injury.
- Motoneuron death was quantified at 14 days post-injury.
Main Results:
- Intrathecal siRNA effectively inhibited c-jun mRNA and protein expression in injured motoneurons.
- Knockdown of c-jun significantly augmented the death of injured spinal motoneurons by day 14.
- Intrathecal siRNA delivery proved effective for mediating gene expression in injured motoneurons.
Conclusions:
- Induction of c-jun gene expression plays a critical role in the survival of injured spinal motoneurons.
- Silencing c-jun exacerbates motoneuron loss after spinal root avulsion.
- Intrathecal siRNA is a viable method for modulating gene expression in spinal motoneurons in vivo.
