Developmental changes in the response of murine cerebellar granule cells to nitric oxide.
Nitric oxide is a diffusible messenger that plays a multitude of roles within the nervous system including modulation of cell viability. However, its role in regulating neuronal survival during a defined period of neurodevelopment has never been investigated. We discovered that expression of the messenger RNA for both neuronal and endothelial nitric oxide synthase increased in the early postnatal period in the cerebellum in vivo, whilst the expression of inducible nitric oxide synthase remained constant throughout this time in development. Whilst scavenging of nitric oxide was deleterious to the survival of early postnatal cerebellar granule neurons in vitro, this effect was lost in cultures derived at increasing postnatal ages. Conversely, sensitivity to exogenous nitric oxide increased with advancing postnatal age. Thus, we have shown that as postnatal development proceeds, cerebellar granule cells alter their in vitro survival responses to both nitric oxide inhibition and donation, revealing that the nitric oxide's effects on developing neurons vary with the stage of development studied. These findings have important consequences for our understanding of the role of nitric oxide during neuronal development.
Oldreive
Ceri E
CE
Bute Building, School of Biology, St Andrews, Fife, UK.
Gaynor
Steven
S
Doherty
Gayle H
GH
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III