Ultrastructure of Neuromuscular Junction in Vacor-induced Diabetic Rats

OBJECTIVES: Rodenticide Vacor causes a severe peripheral neuropathy in humans. Electrophysiologic studies on a peripheral motor nerve-skeletal system of Vacor-treated rat showed decreased amplitude of muscle action potential without conduction velocity abnormalities. The ultrastructural studies of the neuromuscular junction were performed to clarify the anatomic site of the Vacor-induced peripheral neuropathy in male Wistar rats. METHODS: After oral administration of a single dose of Vacor, 80 mg/kg of body weight, to the experimental animals, neuromuscular junctions within the interosseous muscles of the hind foot were observed in time. RESULTS: No axon terminal change was noted until 24 hours after the administration of Vacor. Remarkable loss of presynaptic vesicles and swollen endoplasmic reticulum in the axon terminal were developed at 3 days after Vacor treatment. Progressive degenerative changes consisting of marked loss of presynaptic vesicles, focal disruption of membrane in the axon terminal with disappearance of the number of the damaged axon terminal appeared, and flattening of postsynaptic folds was also seen. CONCLUSIONS: These results suggest that degenerative changes in axon terminal at neuromuscular junction may contribute to the peripheral neuropathy developed in the early phase of Vacor poisoning.