EXPRESSION OF NITRIC-OXIDE SYNTHASE BY MOTOR-NEURONS IN THE SPINAL-CORD OF THE MUTANT MOUSE WOBBLER

The expression of nitric oxide synthase (NOS) has been studied in the spinal cord of the mutant mouse wobbler, a recessive mutation in which there is motor neurone degeneration, using nicotinamide dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Abnormal NOS positive l arge neuronal profiles could be found in the ventral horn of affected mutant animals but not their unaffected littermate controls. The numbe r of abnormal profiles observed was dependant upon the age of the anim al. A small number of these NOS positive large neuronal profiles were seen at the onset of the disease at 3-4 weeks of age, larger numbers w ere found in animals aged 5-8 weeks coincident with the main period of motor neurone death, whilst in the spinal cords of older animals aged 9-12 months, when motor neurone death is minimal, none were found. Th ese NOS positive profiles seen in younger wobbler mouse ventral horn h ad a morphology and size similar to that of degenerating motor neurone s seen in Nissl stained preparations. It was concluded that these NOS positive profiles were degenerating motor neurones. These observations provide further evidence that induction of nitric oxide synthase expr ession may play a role in motor neurone death. Though no NOS positive motor neurones were found in the spinal cords of older wobblers increa sed numbers of NOS positive varicose axons were observed in the ventra l horn often forming tangled accumulations on the border of the grey a nd white matter.