Regeneration, Repair, and Developmental NeuroscienceResearch PaperC-jun phosphorylation contributes to down regulation of neuronal nitric oxide synthase protein and motoneurons death in injured spinal cords following root-avulsion of the brachial plexus
Highlights
▶Root-avulsion induces c-jun phosphorylation in spinal cord and inside motoneurons of adult rats. ▶c-jun phosphorylation inhibits nNOS activation and counts for motoneurons death after avulsion. ▶nNOS protein level down to the baseline in spinal cord is harmful for motoneurons to survive avulsion. ▶The phosphorylated c-jun and nNOS are colocalized in injured motoneurons after avulsion. ▶nNOS maybe one of the downstream molecules of c-jun phosphorylation in root-avulsion injury.
Section snippets
Animal surgery
Adult male Sprague–Dawley rats (200–250 g) were bought from the Laboratory Animal Center of Sun Yat-sen University. All procedures related to the care of animals were carried out according to the Chinese National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Committee on the Use of Live Animals in Teaching and Research of Sun Yat-sen University. Animals were housed in environmentally enriched conditions under a 12 h light/dark cycle throughout
Root-avulsion increased the level of c-jun phosphorylation but decreased the level of nNOS in injured spinal cords
The activation of the JNK/c-jun pathway and nNOS in spinal cord tissues following root-avulsion were assessed by a JNK kinase assay and Western blotting from 4 h to 14 days post-injury (Fig. 1). The result of JNK kinase assay showed an obvious change in JNK activity, which increased approximately 1.3 fold from 4 to 12 h and then decreased from 1 to 14 days post-injury in injured spinal cords following root-avulsion (Fig. 1A). Statistical analysis showed that the JNK activity was significantly
Discussion
In the present study, we demonstrated the specific involvement of the JNK/c-jun signal transduction pathway in root-avulsion, and we found that phosphorylation of c-jun contributes to the avulsion-induced reduction of nNOS expression in the injured spinal cord within the first 14 days of root-avulsion. In addition, the present study showed an inverse relationship between phospho-c-jun and nNOS expression in avulsion-injured spinal cords of adult rats. Inhibition of c-jun phosphorylation
Conclusion
The present study provides evidence that JNK/c-jun signaling is involved in brachial root-avulsion. The phosphorylation of c-jun contributed to the avulsion-induced reduction in nNOS gene expression in injured spinal cords within the first 14 days following root-avulsion. The reduction of nNOS below baseline levels in whole injured spinal cords is harmful for injured motoneurons to survive the root-avulsion. Further studies should use siRNA to downregulate c-jun gene expression to determine
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2015, Neural RegenerationRetrograde response in axotomized motoneurons: Nitric oxide as a key player in triggering reversion toward a dedifferentiated phenotype
2014, NeuroscienceCitation Excerpt :Upregulation of c-jun expression preceded induction of nNOS expression in injured motoneurons by 7 days following ventral root-avulsion, and thereafter both proteins colocalized within dying spinal motoneurons (Zhou et al., 2008). Furthermore, c-jun phosphorylation regulates nNOS expression and motoneuron death in injured spinal cords following root-avulsion of the brachial plexus (Wang et al., 2011). Recent findings from differentiated PC12 cells show that experimental c-jun downregulation also reduced nNOS expression (Cheng et al., 2012).
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These authors contributed equally to this work.