Oldreive Ceri E, Gaynor Steven, Doherty Gayle H
Bute Building, School of Biology, St Andrews, Fife, UK.
Neurochem Int. 2008 Jun;52(8):1394-401. doi: 10.1016/j.neuint.2008.02.010. Epub 2008 Mar 18.
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.
一氧化氮是一种可扩散的信使分子，在神经系统中发挥多种作用，包括调节细胞活力。然而，其在特定神经发育阶段调节神经元存活方面的作用从未被研究过。我们发现，在体内小脑出生后早期，神经元型和内皮型一氧化氮合酶的信使核糖核酸表达均增加，而诱导型一氧化氮合酶的表达在整个发育过程中保持恒定。虽然在体外清除一氧化氮对出生后早期小脑颗粒神经元的存活有害，但这种效应在出生后年龄增加时所获得的培养物中消失。相反，对外源性一氧化氮的敏感性随着出生后年龄的增长而增加。因此，我们已经表明，随着出生后发育的进行，小脑颗粒细胞改变了它们对一氧化氮抑制和给予的体外存活反应，这表明一氧化氮对发育中神经元的影响随所研究的发育阶段而变化。这些发现对于我们理解一氧化氮在神经元发育过程中的作用具有重要意义。
