Glial-mediated neuroprotection: Evidence for the protective role of the NO-cGMP pathway via neuron-glial communication in the peripheral nervous system
Glial-mediated neuroprotection: Evidence for the protective role of the NO-cGMP pathway via neuron-glial communication in the peripheral nervous system
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作者：
Thippeswamy, T;McKay, JS;Murphy, D
NO-cGMP 通路已成为参与神经元和神经胶质细胞之间通讯的神经保护信号系统。我们之前已经证明，背根神经节 (DRG) 神经元的轴切术或神经生长因子 (NGF) 剥夺会导致 NO 产生增加，同时卫星胶质细胞中 cGMP 产生增加。阻断 NO 或其受体、cGMP 合成酶可溶性鸟苷酸环化酶 (sGG)，会导致神经元和神经胶质细胞凋亡。我们现在表明，将新生儿 DRG 神经元与用 NO 供体或膜渗透性 cGMP 类似物预处理的雪旺细胞或在相同 Nvay 处理的雪旺细胞培养物的培养基中维持的神经元进行共培养，可防止神经元凋亡。 NO 供体和 cGMP 治疗。雪旺细胞的合成导致 NGF 和 NT3 的合成。此外。如果施万细胞先前被表达显性失活 sGC 突变转基因的腺病毒载体感染，则用 NO 供体处理这些施万细胞现在无法防止神经元凋亡。以这种方式处理的雪旺细胞也不能表达 cGMP 或神经营养素。这些发现表明施万细胞介导的 NO-sGG-cGMP 介导的 NGF 和 NT3 合成可保护神经元。 (C) 2004 Wiley-Liss, Inc.
The NO-cGMP pathway has emerged as a neuroprotective Singaling system involved in communication between neurons and glia. We have previouSly-shown that axotomy or nerve growth factor (NGF)-deprivation of dorsal root ganglion (DRG) neurons leads to increased production of NO and at the same time an increase in cGMP production in their satellite glia cells. Blockade of NO or its receptor, the cGMP synthesizing enzyme soluble guanylate cyclase (sGG), results in apoptosis of neurons and glia. We now show that co-culture of neonatal DRG neurons with either Schwann cells pre-treated with an NO donor or a, membrane-permeant cGMP analogue: or neurons maintained in the medium from Schwann cell cultures treated in the Same Nvay: prevents neuronal apoptosis. Both NO donor and cGMP treatment. of Schwann cells results in synthesis of NGF and NT3. Furthermore. if the Schwann cells are previously infected with adenoviral vectors expressing a dominant negative sGC mutant transigene, treatment of these Schwann cells with an NO donor now fails to prevent, neuronal apoptosis. Schwann cells treated in this way also fail to express neither cGMP nor neurotrophins. These findings suggest NO-sGG-cGMP-mediated NGF and NT3 Synthesis by Schwann cells protect neurons. (C) 2004 Wiley-Liss, Inc.