NOS/CGKI PATHWAY AND DEVELOPMENT OF CHICK DRG

一氧化氮（NO）是生理功能的主要调节剂。它可以 通过激活鸟苷酰间接激活cGMP依赖性激酶（cGK 环化酶研究表明，NO和cGks可能在感觉神经系统中发挥作用， 信号和发展。神经元型一氧化氮合酶（NOS）是一种短暂的 在大鼠胚胎中由背根神经节（DRG）神经元表达。在 此外，cGKI也被定位于DIG神经元的亚群， 大鼠然而，这两种酶在DRG中可能发挥的实际作用 发展尚未研究。 最近的研究已经确定了NO在神经毒性中的作用。NO与 过氧化物形成过氧硝酸盐。这种过氧硝酸盐被认为会诱导 皮质细胞或PC 12细胞凋亡或坏死。还已经 显示NO阻止DRG神经元培养物中神经突的生长。 因此，NOS/cGK通路可能在DRG中起作用 通过调节细胞存活和轴突生长来促进发育。 这项建议旨在利用鸡胚作为研究 NOS和cGK的激活剂和抑制剂在发育过程中的作用。的 第一组实验集中于确定时间表达 鸡背根神经节NOS和cGKI的表达。使用这些结果，第二组 实验将确定NOS和cGKI在存活和神经突生长中的作用。 培养DRG的产物。第三组实验使用药理学 用于阐明NOS/cGKI途径在鸡发育中的作用的试剂 体内DRG。综合起来，结果形成了三组实验 将阐明NOS/cGK在DRG发育中的作用。

Nitric oxide (NO) is a major regulator of physiological function. It can indirectly activate cGMP-dependent kinase (cGK) by activating guanylyl cyclase. Reports suggest that NO and cGks may play a role in sensory signaling and development. Neuronal NO synthase (NOS)is transiently expressed by dorsal root ganglia (DRG) neurons in the rat embryo. In addition, cGKI has also been localized to a subpopulation of DIG neurons in rats. However, the actual role that these two enzymes may play in DRG development has not been studied. Recent studies have defined a role for NO in neurotoxicity. NO reacts with superoxide to form peroxynitrate. This peroxynitrate is thought to induce apoptosis or necrosis in cortical cells or PC12 cells. It has also been shown that NO halts the growth of neurites in cultures of DRG neurons. Thus, it is possible that the NOS/cGK pathway plays a role in DRG development by regulating cell survival and axon outgrowth. This proposal aims to use the chick embryo as a model for studying the effects of activators and inhibitors of NOS and cGK during development. The first set of experiments are focused at determining the temporal expression of NOS and cGKI in chick DRG. Using these results , the second set of experiments will define the role for NOS and cGKI in survival and neurite outgrowth of cultured DRG. The third set of experiments use pharmacological agents to elucidate a role for the NOS/cGKI pathway in development of chick DRG in vivo. Taken together, the results form the three sets of experiments will elucidate NOS/cGK function in developing DRG.