REGULATION OF ABERRANT NEUROFILAMENT PHOSPHORYLATION IN NEURONAL PERIKARYA .4. EVIDENCE FOR THE INVOLVEMENT OF 2 SIGNALS

Axonal regeneration over long distances is dependent upon events occur ring both in the distal stump and in the neuronal cell body. Little is known concerning how events in the distal stump influence the cell bo dy response to injury, or the axon reaction. In the present study, we examined this relationship for one component of the axon reaction (i.e . aberrant neurofilament (NF) phosphorylation) in the C57BL/Ola (Ola) mouse mutant, a model which exhibits delayed Wallerian degeneration (u p to 3 weeks) and retarded regeneration of sensory neurons. Non-axotom ized normal (C57/6J/BL) and Ola mice demonstrated modest immunostainin g to phosphorylated NF (pNF) epitopes (using monoclonal antibody 06-17 ) in some (11%) L4 dorsal root ganglion (DRG) neuronal cell bodies. In normal mice, modest to intense immunoreactivity was present in 43% of DRG neurons at 1 week following a sciatic nerve crush (axotomy). The intensity and extent of staining declined with reinnervation, being re duced slightly at 2 weeks and more notably by 3 weeks following axotom y. In Ola mice, the intensity and extent (43%) of staining were not di fferent from normal axotomized mice at 1 week following axotomy. Howev er, the intensity was less and the extent of staining reduced by 28% a t 2 weeks following axotomy. By 3 weeks, staining levels were again in creased, being similar to that observed in Ola and normal mice at 1 we ek following axotomy. Taken together, the results suggest that aberran t expression of pNF epitopes in DRG neuronal cell bodies is regulated by at least two signals. The first signal is not dependent upon proces ses associated with Wallerian degeneration since pNF expression is ful ly developed in Ola mice when the vast majority of fibers remain intac t. This suggests that induction arises from the loss of a target tissu e-derived retrogradely transported trophic signal. The presence of a s econd signal is suggested by the failure of Ola mice to maintain (at 2 weeks) the level of pNF expression. This indicates that events in the distal stump may influence both the magnitude and duration of the axo n reaction.