Expression of nitric oxide synthase by motor neurones 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 large neuronal profiles could be found in the ventral horn of affected mutant animals but not their unaffected littermate controls. The number of abnormal profiles observed was dependant upon the age of the animal. 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 were 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. These NOS positive profiles seen in younger wobbler mouse ventral horn had a morphology and size similar to that of degenerating motor neurones 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 expression may play a role in motor neurone death. Though no NOS positive motor neurones were found in the spinal cords of older wobblers increased numbers of NOS positive varicose axons were observed in the ventral horn often forming tangled accumulations on the border of the grey and white matter.