title: Effects of nitric oxide on the survival and neuritogenesis of cerebellar Purkinje neurons.
abstract: Nitric oxide has been investigated widely both during neurodevelopment and in neurological diseases. However, whilst it has been established that nitric oxide-producing enzymes of nitric oxide synthase family are expressed in cerebellar Purkinje neurons, the effects of nitric oxide on the viability and morphology of these neurons remain unknown. Here, we have demonstrated that the activity of neuronal nitric oxide synthase, but not the inducible or endothelial forms of this enzyme, is required to support the survival of a proportion of cerebellar Purkinje neurons in vitro. We discovered that donation of high concentrations of exogenous nitric oxide reduces Purkinje neuron survival in culture and that peroxynitrite is also toxic to these cells. Finally, we demonstrated that exogenous nitric oxide and peroxynitrite reduce both the magnitude and the complexity of the neurite arbour extended by cerebellar Purkinje neurons. Taken together, these findings reveal that whilst a low level of endogenous nitric oxide, released by the activity of neuronal nitric oxide synthase, is beneficial to cerebellar Purkinje neurons in vitro, high levels of exogenous nitric oxide and peroxynitrite are detrimental to both the survival of these neurons and to their ability to extend processes and form functional neural networks.
authors: School of Biology, University of St Andrews, Bute Medical Buildings, St. Mary's Quad, St Andrews, Fife, Scotland, KY16 9TS, UK.
authors: Ceri E
authors: CE
authors: Oldreive
authors: Steven
authors: S
authors: Gaynor
authors: Gayle Helane
authors: GH
authors: Doherty
mesh_terms: D000818:Animals; D001565:Benzoates / Q000633:toxicity; D002452:Cell Count; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D002525:Cerebellar Cortex / Q000166:cytology / Q000196:embryology; D002956:Citrulline / Q000031:analogs & derivatives / Q000633:toxicity; D005260:Female; D007093:Imidazoles / Q000633:toxicity; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000494:pharmacology / Q000633:toxicity*; D020030:Nitric Oxide Donors / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D009603:Nitroso Compounds / Q000633:toxicity; D030421:Peroxynitrous Acid / Q000633:toxicity; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D026361:Reactive Nitrogen Species / Q000633:toxicity; D013890:Thiourea / Q000031:analogs & derivatives / Q000633:toxicity
chemical_list: D001565:Benzoates; D007093:Imidazoles; C093285:NOC 18; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D026361:Reactive Nitrogen Species; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D030421:Peroxynitrous Acid; D007550:Isothiuronium; D002956:Citrulline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium; D013890:Thiourea; C086717:S-methylthiocitrulline