TYPE-I NITRIC-OXIDE SYNTHASE FULLY ACCOUNTS FOR NADPH-DIAPHORASE IN RAT STRIATUM, BUT NOT CORTEX

The novel gaseous neuromediator nitric oxide is thought to play an important role in development and plasticity.(20) Despite this, gene-knockout mice lacking neuronal (Type I) nitric oxide synthase exhibit relatively normal brain development and behavior. The nervous system of these mice (especially the forebrain) retains some calcium-dependent nitric oxide synthesis, presumably reflecting other isozymes.(8) Type I nitric oxide synthase has NADPH-dependent diaphorase activity.(2,3,7,16) However, this stain also recognizes other isozymes,(18,23) and it remains controversial whether all diaphorase-positive neurons contain Type I nitric oxide synthase.(13,22) To assess whether neurons containing another isoform of nitric oxide synthase may be present in the forebrain of normal rodents, we studied co-localization of diaphorase staining with immunocytochemistry for Type I nitric oxide synthase. Co-localization was complete in the striatum, but some neurons deep in cortex were diaphorase-positive and immunonegative, and therefore may contain a splice variant(15) or novel isozyme of nitric oxide synthase.