Ultrastructural alterations of the rabbit sciatic nerve, spinal cord and cerebellum, following methionine sulphoximine administration

Abstract

Methii~nine suluhoximine (MSO) is a centrally ácting neurutoxin wh'ich inhibits the glutainate nietabolism enzymes and has convulsive properties. Sniall doses of MSO were administered to rabbits. either intra\,eiiously (IV) or intracerebroventricularly (ICV), anil electron microscopic examination of the cerebellum. the spinal cord and the sciatic nerve was perforined on the first day of rabbit hind leg rigid paralysis (myopathy with histvlogical findings resenibling myositis). which set in by [he 2nd to 4th day after MSO administration. In thc cerebelluin focal minor alterations were hund in the astrocytes (swelling and lucidity. diminution of glycogen graiiules) and sparsely in the presynaptic terminals (luciditj. and clumping). whereas inost of the neuron prescnted a nornial appearance. In the spinal cord and in the sciatic nerve a dissociation of the axon from the iiiyelin shcath was evident in a small number of niyelinatcd nerve fibres, along with the appearance of vacuolated spaces. Mitochondrial disorganisation in the axons. as well as glial cell alterations, were also seen. Th c u l t r a s t r u c t ~ ~ r aall terat ions we r e non spe c i f i c , Lind siiice they wcre induced 2 to 4 days after the adniiriistration of either minimum doses (IV) or of exti-cmely low doses (ICV) of MSO, they inay be attributed to the inordinate increase of metabolism during the period of convulsions.