NEUROTOXIC EFFECTS OF 2,5-HEXANEDIONE IN RATS - EARLY MORPHOLOGICAL AND FUNCTIONAL-CHANGES IN NERVE-FIBERS AND NEUROMUSCULAR-JUNCTIONS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 2  (1) , 25-32
Abstract
Changes occurring in the early stages of neurotoxicity induced by an intensive treatment with 2,5-hexanedione were studied. Rats were injected i.p. each day with 450 mg/kg of body wt for the 1st 14 days and then with 300 mg/kg for an additional 20 days. After 34 days of treatment typical axonal lesions were observed in sciatic branches, together with electrophysiological signs of denervation in several fibers of leg muscles. Morphological changes were found in axons of spinal cord and optic tracts. At an earlier stage (days 13-18), when clinical signs appeared, in the absence of morphological changes in peripheral nerves and denervated muscle fibers, significant alterations in functioning of several neuromuscular junctions were observed: increased frequency and amplitude of miniature end-plate potentials, reduction of mean quantal content of evoked end-plate potential (epp) and absence of epp in some fibers. Changes indicated a progressive functional impairment of nerve terminals which could represent a primary alteration of membrane resting and action potentials and a secondary effect of changes in axonal transport. Both these hypothetical events could result from inhibition of glycolytic enzymes of nervous tissue by 2,5-hexanedione.