Peripheral neuropathy is a significant complication of diabetes resulting in increased patient morbidity and mortality. Deficiencies of neurotrophic substances (e.g. NGE NT-3, and
IGF-I) have been proposed as pathogenetic mechanisms in the development of distal symmetrical sensory
diabetic polyneuropathy, and salutary effects of exogenous
NGF administration have been reported in animal models. In comparison, relatively little is known concerning the effect of
NGF on experimental diabetic sympathetic autonomic neuropathy. We have developed an experimental animal model of
diabetic autonomic neuropathy characterized by the regular occurrence of pathologically distinctive dystrophic axons in prevertebral sympathetic ganglia and ileal mesenteric nerves of rats with chronic
streptozotocin (STZ)-induced diabetes. Treatment of STZ-diabetic rats for 2-3 months with pharmacologic doses of
NGF or NT-3, neurotrophic substances with known effects on the adult sympathetic nervous system, did not normalize established
neuroaxonal dystrophy (
NAD) in diabetic rats in the prevertebral superior mesenteric ganglia (SMG) and ileal mesenteric nerves as had pancreatic islet
transplantation and
IGF-I in earlier experiments.
NGF treatment of control animals actually increased the frequency of
NAD in the SMG. New data suggests that, in adult sympathetic ganglia.
NGF may contribute to the pathogenesis of
NAD rather than its amelioration, perhaps as the result of inducing intraganglionic axonal sprouts in which dystrophic changes are superimposed. NT-3 administration did not alter the frequency of
NAD in diabetic animals, although it resulted in a significant decrease in
NAD in control SMG. Although deficiencies of neurotrophic substances may represent the underlying pathogenesis of a variety of experimental neuropathies, delivery of excessive levels of selected substances may produce untoward effects.