DELAYED WALLERIAN DEGENERATION AND INCREASED NEUROFILAMENT PHOSPHORYLATION IN SCIATIC-NERVES OF RATS WITH STREPTOZOCIN-INDUCED DIABETES

It is known that Wallerian degeneration (WD) is prerequisite for nerve regeneration, which is impaired in experimental diabetic rats. To elu cidate the effect of hyperglycemia on WD, we studied the time course o f WD after axotomy in streptozocin-diabetic (DM) and control rats. Sci atic nerves were removed at several time points after axotomy (clays 0 -24). Morphometric analysis indicated that WD was delayed in DM throug hout experimental period. Quantitative immunohistochemical analysis sh owed that the early recruitment of macrophage did not differ between t he two groups, although its late recruitment was significantly decreas ed in DM at 15 and 24 days post-axotomy, which suggested that the macr ophage-associated process did not contribute to delayed WD in diabetes . Immunoblot analysis showed a delay in the degradation of neurofilame nts (NFs) in DM during WD. Phosphorylated NFs detected by SMI31 were m ore recognized in DM, while the opposite was true for unphosphorylated NFs detected by SMI32. Since it is known that the sensitivity of NF t o calpain-mediated proteolysis is modulated by its carboxyl-terminal p hosphorylation state and phosphorylated NFs are resistant to calpains, we concluded that abnormal NF phosphorylation state in diabetes could be one of the mechanisms by which axonal degeneration was delayed. (C ) 1998 Elsevier Science B.V.