Eph/ephrin信号通路与脑神经发生的综述

神经药理学报 ›› 2014, Vol. 4 ›› Issue (1): 25-28.

Eph/ephrin信号通路与脑神经发生的综述

刘婷婷，王文

首都医科大学宣武医院药物研究室，教育部神经变性病学重点实验室，北京市老年病医疗研究中心，北京，100053，中国

出版日期:2014-02-26 发布日期:2014-06-06
通讯作者: 王文，男，教授，博士，研究生导师；研究方向：神经药理，中药药理；E-mail:lzwwang@163.com
作者简介:刘婷婷，女，硕士研究生；研究方向：神经药理，中药药理；E-mail:liuting_416@126.com
基金资助:
“重大新药创制”科技重大专项(No.2012ZX09102-201-016)，国家自然科学基金(No.81173575\81373994)，北京市自然科学基金(No.7062031)，北京市教委科技创新平台项目(No.111219)，2011年北京市卫生系统高层次卫生技术人才培养计划项目（No.2011-3-097)，第52批中国博士后基金(No.106455)

Eph/ephrin Signaling Pathway in Brain Neurogenesis

LIU Ting-ting, WANG Wen

Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing Geriatric Medical Research Center, Beijing, 100053, China

Online:2014-02-26 Published:2014-06-06
Contact: 王文，男，教授，博士，研究生导师；研究方向：神经药理，中药药理；E-mail:lzwwang@163.com
About author:刘婷婷，女，硕士研究生；研究方向：神经药理，中药药理；E-mail:liuting_416@126.com
Supported by:
“重大新药创制”科技重大专项(No.2012ZX09102-201-016)，国家自然科学基金(No.81173575\81373994)，北京市自然科学基金(No.7062031)，北京市教委科技创新平台项目(No.111219)，2011年北京市卫生系统高层次卫生技术人才培养计划项目（No.2011-3-097)，第52批中国博士后基金(No.106455)

摘要/Abstract

摘要： Eph/ephrin是目前已知的具有最多成员的蛋白受体酪氨酸激酶家族，在机体的发育过程中参与细胞迁移、轴突导向、血管形成及神经网络的形成，对成年中枢神经系统的神经再生和突触可塑性具有重要作用。通过激活或抑制Eph/ephrin可调节损伤后的突触功能和干细胞分化，达到修复梗死灶、改善神经功能缺失的目的。本文对Eph/ephrin信号通路在成年动物海马区、室管膜下区及非传统神经发生区域内调节神经发生、迁移以及突触可塑性作用的研究进展进行综述，将对探索有效的神经损伤修复方法有一定的提示作用。

关键词: Eph/ephrin信号通路, 神经发生, 缺血性脑损伤

Abstract: Eph/ephrin is the largest subfamily of receptor tyrosine kinases, which participate in cell migration, axon guidance, angiogenesis
and the formation of neural network in the development process. Eph/ephrin signaling pathway also plays an important role in neurogenesis and synaptic plasticity of adult nervous system. It has been suggested that neurogenesis can be enhanced after injury by regulating Eph/ephrin signaling pathway to improve neural function. This review summarized the effects of Eph/ephrin signaling
pathway in subventricular zone (SVZ), subgranular zone (SGZ) and nonneurogenic central nervous system (CNS) regions, on neurogenesis, neuronal migration and synaptic plasticity, which provided an insight into developing effective neural repairment approaches.

Key words: Eph/ephrin signaling pathway, neurogenesis, ischemic brain injury

刘婷婷, 王文. Eph/ephrin信号通路与脑神经发生的综述[J]. 神经药理学报, 2014, 4(1): 25-28.

LIU Ting-ting, WANG Wen. Eph/ephrin Signaling Pathway in Brain Neurogenesis[J]. ACTA NEUROPHARMACOLOGICA, 2014, 4(1): 25-28.

参考文献

[1] 左玮, 王起忠, 季晖, 等. Wnt信号对神经发生和血管新生的调控[J]. 中国康复理论与实践, 2011, 17(3): 243-246.

[2] 武菲,张秋玲. 神经干细胞与脑卒中后的神经发生[J]. 生理科学进展, 2012 43(3): 221-225.

[3] Daisuke Nakayama, Tomohiro Matsuyama, Hatsue Ishibashi-Ueda, et al. Injury-induced neural stem/progenitor cells in post stroke human cerebral cortex [J]. J European Neuroscience, 2010, 31(1): 90-98.

[4] Steven G. Kernie, Jack M. Parent. Forebrain neurogenesis after focal ischemic and traumtic brain injury [J]. Neurobiol Disease, 2010, 37(2): 267-274.

[5] 韩莹, 李磊. 缺血性脑损伤中神经发生的研究进展[J]. 神经损伤与功能重建, 2011, (3): 213-215.

[6] Juha-Pekka Himanen, Nayanendu Saha, Dimitar B Nikolov. Cell–cell signaling via Eph receptors and ephrins [J]. Science Direct, 2007, 19: 534-542.

[7] Luo Hong-yu, Yu Guang, Wu Yu-lian, et al. EphB6 crosslinking results in costimulation of T cells [J]. Clinical Investigation, 2002, 110(8): 1141-1150.

[8] Ombretta Salvucci, Giovanna Tosato. Essential roles of EphB receptors and EphrinB ligands in endothelial cell function and angiogenesis [J]. Advances in Cancer Research, 2012, 114: 21-57.

[9] 余剑, 曾进圣. Eph/ephrin与中枢神经可塑性[J]. 中国临床康复, 2002, 6(21): 3198-3199.

[10] Keith K. Murai, Elena B. Pasquale. Eph receptors and ephrins in neuron–astrocyte communication at synapses [J].Glia, 2011, 59(11): 1567-1578.

[11] Peter W. Janes, Bettina Griesshaber, Lakmali Atapattu, et al. Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors [J]. J Cell Biology, 2011, 195(6): 1033-1045.

[12] Mark G. Coulthard, Michael Morgan, Trent M. Woodruff, et al. Eph/ephrin signaling in injury and inflammation [J]. Am J Pathol, 2012, 181(5): 1493-1503.

[13] Fiona Doetsch, Arturo Alvarez-Buylla, Jose-Manuel Garcia-Verdugo, et al. Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone [J]. Nature, 2000, 3(11): 1091-1097.

[14] Mark Katakowski, Zheng-gang Zhang, Ana C. deCarvalho, et al. EphB2 induces proliferation and promotes a neuronal fate in adult subventricular neural precursor cells [J]. Neurosci Lett, 2005, 385(3): 204-209.

[15] Michelle H. Theus, Jerome Ricard, John R. Bethea, et al. EphB3 limits the expansion of neural progenitor cells in the subventricular zone by regulating p53 during homeostasis and following traumatic brain injury [J]. Stem Cells, 2010, 28(7): 1231-1242.

[16] Jerome Ricard, Jessica Salinas, Lissette Garcia, et al. EphrinB3 regulates cell proliferation and survival in adult neurogenesis [J]. Mol Cell Neurosci, 2006, 31(4): 713-722.

[17] Kara del Valle, Michelle H. Theus, John R. Bethea, et al. Neural progenitors proliferation is inhibited by EphB3 in the developing subventricular zone [J]. Int J Dev Neurosci, 2011, 29(1): 9-14 .

[18] Johan Holmberg, Annika Armulik, Kirsten-André Senti, et al. Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis [J]. Genes Dev, 2005, 19(4): 462-471.

[19] Jenny Lauterbach, Rüdiger Klein. Release of full-length EphB2 receptors from hippocampal neurons to cocultured glial cells [J]. J Neurosci, 2006, 26(45): 11575-11581.

[20] Randolph S Ashton, Anthony Conway, Chinmay Pangarkar, et al. Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling [J]. Nature Neuroscience, 2012, 15(10): 1399-1408.

[21] Michael J. Chumley, Timothy Catchpole, Robert E. Silvany, et al. EphB receptors regulate stem/progenitor cell proliferation, migration and polarity during hippocampal neurogenesis [J]. Neurosci, 2007, 27(49): 13481-13490.

[22] Jian-guo Li, Nai-hong Liu, Ye Wang, et al. Inhibition of EphA4 signaling after ischemia–reperfusion reduces apoptosis of CA1 pyramidal neurons [J]. Neurosci Lett, 2012, 518(2): 92-95.

[23] Jian-wei Jiao, David A. Feldheim, Dong Feng Chen. Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system [J]. Proc Natl Acad Sci USA, 2008, 105(25): 8778-8783.

[24] Andrew C. McClelland, Martin Hruska, Andrew J. Coenen, et al. Trans-synaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling [J]. Proc Natl Acad Sci USA, 2010, 107(19): 8830-8835.

[25] Alma Rodenas-Ruano, Miguel A. Perez-Pinzon, Edward J. Green, et al. Distinct roles for ephrinB3 in the formation and function of hippocampal synapses [J]. Dev Biol, 2006, 292(1): 34-45.

[26] Antonio Trabalza, Sandra Colazingari, Carmelo Sgobio, et al. Contextual learning increases dendrite complexity and EphrinB2 levels in hippocampal mouse neurons [J]. Behav Brain Res, 2012, 227(1): 175-183.

[27] Keith K. Murai, Louis N. Nguyen, Fumitoshi Irie, et al. Control of hippocampal dendritic spine morphology through ephrinA3/EphA4 signaling [J]. Nat Neurosci, 2003, 6(2): 153-160.

[28] 刘靖, 曲静, 徐晓静, 等. 神经干细胞迁移的研究进展[J]. 中国细胞生物学学报, 2012, 34(3): 201-211.

[29] David G.Wilkinson. How attraction turns to repulsion [J]. Nature Cell Biology. 2003, 5(10): 851-853.

[30] Alexei Poliakov, Maria L. Cotrina, Andrea Pasini, et al. Regulation of EphB2 activation and cell repulsion by feedback control of the MAPK pathway [J]. J Cell Biol, 2008, 183(5): 933-947.

[31]Geraldine Zimmer, Patricia Garcez, Judith Rudolph, et al. Ephrin-A5 acts as a repulsive cue for migrating cortical interneurons [J]. Eur J Neurosci, 2008, 28(1): 62-73.

[32] Judith Rudolph, Geraldine Zimmer, André Steinecke, et al. Ephrins guide migrating cortical interneurons in the basal telencephalon [J]. Cell Adhesion & Migration, 2010, 4(3): 400-408.