Effect of NGF and neurotrophin-3 treatment on experimental diabetic autonomic neuropathy

Robert E. Schmidt, Denise A. Dorsey, Lucie N. Beaudet, Curtis A. Parvin, Enrique Escandon

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Peripheral neuropathy is a significant complication of diabetes resulting in increased patient morbidity and mortality. Deficiencies of neurotrophic substances (e.g. NGF, 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.

Original languageEnglish
Pages (from-to)263-273
Number of pages11
JournalJournal of neuropathology and experimental neurology
Volume60
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Autonomic Neuropathy
  • Diabetes
  • Neuroaxonal dystrophy
  • Sympathetic ganglia

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