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

Abstract

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.

• Authors: R E Schmidt, D A Dorsey, L N Beaudet, C A Parvin, E Escandon
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 60 Issue 3 Pg. 263-73 (Mar 2001) ISSN: 0022-3069 [Print] England
• PMID: 11245210 (Publication Type: Journal Article)

Chemical References

• Neurotrophin 3
• Nerve Growth Factor

Topics

• Animals
• Axons (drug effects, pathology)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetic Neuropathies (drug therapy, pathology)
• Disease Models, Animal
• Ganglia, Sympathetic (drug effects, pathology, ultrastructure)
• Intestines (innervation)
• Male
• Microscopy, Electron
• Nerve Growth Factor (metabolism, pharmacology)
• Neurotrophin 3 (metabolism, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Superior Cervical Ganglion (drug effects, pathology)
• Sympathetic Fibers, Postganglionic (drug effects, pathology, ultrastructure)