Neurotrophin-3 reverses nerve conduction velocity deficits in streptozotocin-diabetic rats

The ability of neurotrophin-3 (NT-3) to reverse established nerve disorders was investigated in the peripheral neuraxis of streptozotocin-diabetic rat s. Sciatic sensory and motor nerve conduction velocity deficits established after 2 months of diabetes were completely normalized by one further month of treatment with either NT-3 or insulin. None of these conduction velocit y changes were associated with altered mean axonal caliber in the sciatic n erve. In the dorsal and ventral roots, mean axonal caliber was significantl y decreased after 8 weeks of diabetes (both P < 0.05). Subsequently, one mo nth of insulin, but not NT-3, treatment increased mean axonal caliber to ag e-matched control values. NT-3 treatment was also without effect on the sig nificant (both P < 0.05) decrease in phosphorylated heavy neurofilament (NF H) subunits seen in dorsal and ventral roots of 12 week diabetic rats. In t he sural nerve, diabetes attenuated a maturation-associated increase in mea n axonal caliber over the first 8 weeks of diabetes, and induced atrophy be tween weeks 8 and 12 that was ameliorated by both NT-3 and insulin treatmen t, Reductions in sural nerve axonal caliber were associated with a tendency for elevation of both phosphorylated NFH levels in large fibers and the ra tio of phosphorylated to nonphosphorylated NFH that was attenuated by NT-3. These data demonstrate that NT-3 corrects established sciatic nerve conduc tion deficits in diabetic rats in a manner independent of changes in axonal caliber in this nerve. Further, although NT-3 was without effect on decrea ses in axonal caliber and NFH subunit phosphorylation in the spinal roots, reversal of axonal caliber deficits in peripheral nerves of sensory fibers may involve NT-3-mediated normalization of aberrant neurofilament phosphory lation.