Differences in c-jun and nNOS expression levels in motoneurons following different kinds of axonal injury in adult rats

Abstract

In the peripheral nervous system (PNS), root avulsion causes motoneuron degeneration, but the majority of motoneurons can survive axotomy. In order to study the mechanism of motoneuron degeneration, we compared the expression patterns of c-jun and neuronal nitric oxide synthase (nNOS), the well-known molecular players in PNS regeneration and degeneration, among adult rats having undergone axotomy (Ax), avulsion (Av), or pre-axotomy plus secondary avulsion (Ax + Av) of the brachial plexus. Our results showed that the highest and longest-lasting c-jun activation occurred in Ax, which was much stronger than those in Av and Ax + Av. The time course and intensity of c-jun expression in Ax + Av were similar to those in Av except on day 1, while the pre-axotomy condition resulted in a transient up-regulation of c-jun to a level comparable to that in Ax. Axotomy alone did not induce nNOS expression in motoneurons. Pre-axotomy left-shifted the time course of nNOS induction in Ax + Av compared to that in Av. Motoneuron loss was not evident in Ax, while it was 70% in Av and more than 85% in Ax + Av at 8 weeks postinjury. The survival of motoneurons was positively correlated with c-jun induction, but not with nNOS expression in motoneurons. Moreover, c-jun induction was negatively correlated with nNOS induction in injured motoneurons. Our results indicate that functional crosstalk between c-jun and nNOS might play an important role in avulsion-induced motoneuron degeneration, while c-jun might act as a prerequisite survival factor and nNOS might act as a predictor for the onset of motoneuron degeneration.

Suppression of c-jun influences nNOS expression in differentiated PC12 cells

“…Compromised proteasome degradation elevates nNOS levels and induces programmed cell death in differentiated PC12 cells (9). In our previous study, there may have been a functional crosstalk between c-jun and nNOS in motoneurons, and this may have had an impact on motoneuron degeneration (16). Our study also showed that c-jun phosphorylation acts as the upstream molecule that inhibits the nNOS expression in injured spinal cords within the first 2 weeks after root-avulsion injury.…”

Involvement of phospholipase C-γ in the pro-survival role of glial cell line-derived neurotrophic factor in developing motoneurons in rat spinal cords

“…Data are expressed as a percentage of the internal control. Results were presented as the means ± standard error of the mean of triplicate samples from at least six separate experiments (n=6), as described in our previous studies (4,26,29).…”

Below Level Central Pain Induced by Discrete Dorsal Spinal Cord Injury

“…Studies of recovery of motor function have extensively used ventral root avulsion as a model of SCI (Chu et al, 2009;Penas et al, 2009;Rodrigues Hell et al, 2009;Scorisa et al, 2009;Su et al, 2009;Zhou et al, 2008), with to our knowledge only one prior article considering root avulsion and allodynia (Bigbee et al, 2007). In that paper, Bigbee and associates avulsed L6ÀS1 ventral roots from the spinal cord and measured at-level (the L5 dermatome level) mechanical allodynia and thermal hyperalgesia in the hindpaw.…”