PATTERNS OF NITRIC-OXIDE SYNTHASE AT THE MESSENGER-RNA AND PROTEIN-LEVELS DURING EARLY RAT-BRAIN DEVELOPMENT

There is substantial evidence that the intra- and intercellular messen ger nitric oxide, generated enzymatically from L-arginine by nitric ox ide synthase in different isoforms, is involved in the development of nervous tissue. In this study we investigated the nitric oxide express ion in the pre- and postnatally developing rat brain. With regard to m essenger RNA, all of the basic nitric oxide synthase isoforms (neurona l, endothelial and macrophage nitric oxide synthase) were already expr essed at embryonic day 10 and showed a temporary decrease at embryonic day 17. Western blot analysis of the three isoform proteins revealed a time pattern that was different from those of messenger RNAs. Althou gh the endothelial nitric oxide synthase isoform was also expressed at embryonic day 10, no quantitative changes were observed over the whol e time period studied. Protein amounts of brain and inducible nitric o xide synthase were first detectable at embryonic day 15, with a tenden cy to rise. A parallel time pattern was found for the NADPH-diaphorase activity in our light microscopic studies, whereas ultrastructurally the reaction product was seen in the brain pallium even of 13-day-old embryos. The data indicate a permanent presence of the transcripts for all nitric oxide synthase isoforms in the rat central nervous system from embryonic day 10 onwards, although the expression of respective p roteins and staining patterns may differ. Copyright (C) 1996 IBRO. Pub lished by Elsevier Science Ltd.