School of Biology, University of St Andrews, Bute Medical Buildings, St. Mary's Quad, St Andrews, Fife, Scotland, KY16 9TS, UK.
J Mol Neurosci. 2012 Feb;46(2):336-42. doi: 10.1007/s12031-011-9590-7. Epub 2011 Jul 5.
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.
一氧化氮在神经发育和神经疾病中都得到了广泛的研究。然而，虽然已经确定一氧化氮合酶家族的产生一氧化氮的酶在小脑浦肯野神经元中表达，但一氧化氮对这些神经元的存活和形态的影响尚不清楚。在这里，我们已经证明，神经元型一氧化氮合酶的活性，而不是该酶的诱导型或内皮型，是支持体外小脑浦肯野神经元存活所必需的。我们发现，高浓度外源性一氧化氮的捐赠会减少培养物中浦肯野神经元的存活，而过氧亚硝酸盐对这些细胞也是有毒的。最后，我们证明外源性一氧化氮和过氧亚硝酸盐降低了小脑浦肯野神经元延伸的轴突树突的幅度和复杂性。总之，这些发现表明，虽然由神经元型一氧化氮合酶活性释放的低水平内源性一氧化氮对体外小脑浦肯野神经元有益，但高水平的外源性一氧化氮和过氧亚硝酸盐对这些神经元的存活及其延伸过程和形成功能性神经网络的能力都是有害的。
