Methods: Autoradiography with [3H]nitro-L-arginine (3HL-NNA) was used to quantify nitric oxide synthase (NOS), and immunocytochemistry to identify NOS isoforms, in spinal cord in amyotrophic lateral sclerosis (ALS) and controls.
Results: In controls NOS binding was marked only in the superficial dorsal horn, but in ALS tissue it was intense throughout the grey and white matter. A single population of binding sites was indicated in controls, but two populations in ALS. In the controls intense neuronal NOS (nNOS) immunoreactivity was present in numerous cells in the dorsal horn, and faint immunoreactivity in small and medium-sized cells in the ventral horn. Only weak immunoreactivity for inducible NOS (iNOS) and endothelial NOS (eNOS) was detectable in control tissue. In ALS, the pattern was broadly similar in the grey matter, but immunoreactivity for both nNOS and iNOS was present in white matter.
Conclusion: Expression of abnormal variants of nNOS or increased expression of iNOS may have a role in motoneuron death in ALS.