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

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.