Co-culturing improves the OGD-injured neuron repairing and NSCs differentiation via Notch pathway activation
Co-culturing improves the OGD-injured neuron repairing and NSCs differentiation via Notch pathway activation
复制标题
共培养通过 Notch 通路激活改善 OGD 损伤的神经元修复和 NSC 分化。
DOI：
10.1016/j.neulet.2013.11.027
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发表时间：
2014-01-24
影响因子：
2.5
通讯作者：
Liu, Xinfeng
中科院分区：
文献类型：
--
作者：
Liu, Qian;Fan, Xinying;Liu, Xinfeng
神经干细胞移植治疗缺血性脑卒中可通过损伤神经元与移植的神经干细胞之间的细胞间串导修复神经元损伤并替代丢失的神经元。本实验建立氧葡萄糖剥夺（OGD）损伤神经元与NSCs体外共培养体系，探讨其对神经元的修复作用及对NSCs分化的影响。我们关注Notchl通路作为这些效应的可能中介。ogd损伤神经元通过上调DLL1、Notchl胞内结构域（NICD）和下游基因Hes1/5，诱导共培养NSCs中Notchl的激活增加。当Notch通路抑制剂DAPT预处理NSCs时，Notchl的激活被阻断，NSCs分化降低，神经营养作用也被消除。新型共培养系统表明，与OGD损伤神经元共培养的NSCs通过Notchl通路激活诱导分化；这些诱导的NSCs显示出更大的潜力来支持损伤神经元的修复和形成新的神经元。2013爱思唯尔爱尔兰有限公司版权所有。
Neural stem cell (NSC) transplantation for ischemic stroke is expected to repair the neuronal injury and replace the lost neurons through cell-cell cross talk between injured neurons and the transplanted NSCs. Here, we set up an in vitro co-culturing system of oxygen-glucose deprivation (OGD) injured neurons and NSCs to investigate the neuronal repairing effect and effects on NSCs differentiation. We focused on the Notchl pathway as a possible mediator of these effects. OGD-injured neurons induced increased activation of Notchl in co-cultured NSCs, through the up-regulations of the DLL1, the Notchl intracellular domain (NICD) and the down-stream genes Hes1/5. When the NSCs were pre-treated with the Notch pathway inhibitor DAPT, the activation of Notchl was blocked, lower NSCs differentiation was detected and the neurotrophic effect was also abolished. As shown by the novel co-culturing system, the NSCs co-cultured with OGD injured neurons were induced to differentiate through the Notchl pathway activation; and these induced NSCs showed greater potential to support both the repair of injured neurons and form new neurons. (C) 2013 Elsevier Ireland Ltd. All rights reserved.