NT-3 ATTENUATES FUNCTIONAL AND STRUCTURAL DISORDERS IN SENSORY NERVESOF GALACTOSE-FED RATS

The present study investigated the effect of NT-3, a neurotrophin expr essed in nerve and skeletal muscle, on myelinated fiber disorders of g alactose-fed rats. Adult, female Sprague-Dawley rats were fed diets co ntaining complete micronutrient supplements and either 0% D-galactose (control) or 40% D-galactose. Treated controls received 20 mg/kg NT-3 and treated galactose-fed rats received 1, 5, or 20 mg/kg NT-3 three t imes per week by subcutaneous injections. After 2 months, sciatic and saphenous sensory nerve conduction velocity (SNCV) and sciatic motor n erve conduction velocity (MNCV) were measured and the sciatic, sural, peroneal and saphenous nerves and dorsal and ventral roots processed f or light microscopy. Treatment of control animals with NT-3 had no eff ect on any functional or structural parameter. Compared to control val ues, galactose feeding induced a sensory and motor nerve conduction de ficit and a reduction in axonal caliber. Treatment with 5 and 20 mg/kg NT-3 ameliorated deficits in sciatic and saphenous SNCV in galactose- fed rats but had no effect on the MNCV deficit. NT-3 treatment also at tenuated the decrease in mean axonal caliber in the dorsal root and su ral nerve but not in the saphenous nerve, ventral root and peroneal ne rve. These observations show that NT-3 can selectively attenuate the s ensory conduction deficit of galactose neuropathy in a dose-dependent manner that depends only in part on restoration of axonal caliber of l arge-fiber sensory neurons.