Axonal injury and peripheral nerve grafting in the thalamus and cerebellum of the adult rat: upregulation of c-jun and correlation with regenerative potential.

ABSTRACT

The protooncogene c-jun is highly expressed for long periods in axotomized PNS neurons. This may be related to their growth and regeneration. In contrast, axotomized CNS neurons show only a small and transient upregulation of c-jun. It has been suggested that there may be a correlation between this failure to maintain high levels of c-jun expression after axotomy and abortive CNS axonal regeneration. We have studied, by in situ hybridization and immunohistochemistry, the c-jun response after stab wound lesion, and after peripheral nerve grafting in the thalamus and cerebellum of the adult rat. A lesion elicits upregulation of c-jun in thalamic neurons ipsilateral to the lesion. This is most evident and prolonged in neurons such as those of the thalamic reticular nucleus, which have an established propensity to regenerate. After peripheral nerve grafting, the c-jun response in thalamic neurons is enhanced, mostly in neurons which have axons regenerating along the grafts. These neurons also upregulate growth-associated protein 43 (GAP-43). By comparison, injured Purkinje cells of the cerebellum which do not regenerate their axons along a graft, do not upregulate either c-jun or GAP-43, although they increase their expression of p75. Thus CNS neurons able to regenerate their axons along a peripheral nerve graft are those in which c-jun is induced after injury, and c-jun may play a critical role in the control of gene programs for axonal regeneration. Moreover, the observed differences in the ability of CNS neurons to regenerate their axons may relate to a difference in their intrinsic molecular response to axotomy.