Electrical stimulation promotes nerve growth factor-induced neurite outgrowth and signaling
Electrical stimulation promotes nerve growth factor-induced neurite outgrowth and signaling
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DOI：
10.1016/j.bbagen.2013.04.007
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发表时间：
2013-08-01
影响因子：
3
通讯作者：
Chen, Linyi
中科院分区：
文献类型：
--
作者：
Chang, Yu-Jung;Hsu, Che-Ming;Chen, Linyi
背景：神经营养因子是神经发育和再生的重要调节因子。神经生长因子(NGF)治疗已经在各种神经损伤和变性模型中进行了试验。然而，NGF能否到达靶组织并在一定时间内保持有效浓度仍不确定。为了促进神经再生，我们研究了NGF和电刺激(ES)在促进神经再生过程中促进神经突起生长的可能性。方法：PC12细胞种植在透明导电器件上的胶原和氧化铟锡(ITO)涂层区域。然后对细胞进行ES和NGF的联合处理。结果：100 mV/mm的ES联合NGF对PC12细胞的突起生长效果最佳。ES增加了NGF诱导的轴突长度，但减少了轴突分支，表明其主要影响轴突的伸长而不是起始。ES促进轴突生长的机制之一是通过增加NGF诱导的ERK1/2(pERK1/2)的磷酸化和Egr1基因的表达。已有研究表明ES可增加蛋白激酶C(PKC)的活性。我们的结果表明，激活PKC进一步增加了NGF诱导的pERK1/2，从而促进了轴突生长。结论：ES可能通过调节ERK1/2的活性来促进NGF诱导的轴突生长。(C)2013爱思唯尔B.V.保留所有权利。
Background: Neurotrophins are important regulators for neural development and regeneration. Nerve growth factor (NGF) therapy has been tested in various models of neural injury and degeneration. However, whether NGF can reach target tissues and maintain effective concentration for a certain period of time remains uncertain. To facilitate neural regeneration, we investigate the possibility of combining NGF and electrical stimulation (ES) in promoting neurite outgrowth, an essential process during neural regeneration.Methods: PC12 cells were seeded on collagen and indium tin oxide (ITO)-coated area on the transparent conductive devices. Cells were then subjected to the combination of ES and NGF treatment. Neurite outgrowth was compared.Results: Our findings suggest that ES of 100 mV/mm together with NGF provides optimal effect on neurite outgrowth of PC12 cells. ES increases NGF-induced neurite length but reduces neurite branching, indicative of its primary effect on neurite elongation instead of initiation. One mechanism that ES enhances neurite outgrowth is through increasing NGF-induced phosphorylation of ERK1/2 (pERK1/2) and expression of Egr1 gene. ES has previously been demonstrated to increase the activity of protein kinase C (PKC). Our result indicates that activating PKC further increases NGF-induced pERK1/2 and thus neurite outgrowth.Conclusion: It is likely that ES promotes NGF-induced neurite outgrowth through modulating the activity of ERK1/2.General significance: Findings from this study suggest that combining ES and NGF provides a promising strategy for promoting neurite outgrowth. (c) 2013 Elsevier B.V. All rights reserved.