Glial cells of the spinal cord and subcortical white matter up-regulate neuronal nitric oxide synthase in sporadic amyotrophic lateral sclerosis

Several studies have suggested that excessive generation of nitric oxide (N O) may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS ). Recently, a selective induction of the neuronal isoform of nitric oxide synthase (nNOS) in glial cells has been reported in an animal model of fami lial ALS. We therefore examined in postmortem tissue the expression of nNOS in patients with sporadic ALS and patients without any history of neurolog ical disease. Using immunohistochemistry, we found an up-regulation of nNOS in glial cells of the spinal cord and subcortical white matter in ALS pati ents compared to controls. The enhanced glial nNOS expression seen in ALS p atients could conceivably contribute to motoneuronal degeneration through N O-mediated cytotoxic effects. (C) 2001 Academic Press.