吴武田教授最新《自然》子刊解析神经研究新发现

　　

生物通报道：来自美生物制药公司Biogen Idec Inc，中国香港大学解剖学系，脑与认知科学国家重点实验室（State Key Laboratory of Brain and Cognitive Sciences）等研究人员发现了一种治疗中枢神经系统CNS脱髓鞘疾病（demyelinating diseases）的新方法，这种方法的机制即LINGO-1或其途径在体内体外少突胶质细胞（Oligodendrocyte）分化和髓鞘（myelination）中的负调控作用。这一研究成果公布在《Nature Medicine》杂志上。

领导这一研究的是香港大学医学院解剖学系副教授，中山大学客座教授的吴武田教授，其一直致力于神经损伤和再生机制方面的基础研究。

脱髓鞘疾病（demyelinating diseases），譬如多发性硬化症（multiple sclerosis，MS，一种自体免疫性疾病（autoimmune disease），即患者体内的免疫系统无法分辨何者是自己的细胞，何者为外来侵犯物，造成免疫系统攻击自身的组织）的一个重要特征就是神经细胞周围髓鞘（myelin sheath）丢失，这主要是因为中枢神经系统（central nervous system，CNS）中发生了炎症反应和胶质增生（gliosis）。

因此目前的治疗主要是靶向抗炎机制，达到阻碍或延缓疾病扩散的目的，而针对轴突髓鞘质（myelin）的一种方法则提供了抑制以及可能逆转疾病扩散的新治疗方法，之前的研究发现含亮氨酸重复序列和免疫球蛋白结构域的Nogo受体作用蛋白（LRR and Ig domain—containing，Nogo Receptor—interacting protein，LINGO-1）是一种体内体外少突胶质细胞（Oligodendrocyte）分化和髓鞘（myelination）的负调控因子。

在这篇文章中，研究人员利用Lingo1基因敲除或者抗LINGO-1功能的抗体造成LINGO-1功能缺失，结果发现这种缺陷型中实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis）功能复原，这通过生物性轴突完整性增加——弥散张量磁共振成像（magnetic resonance diffusion tensor imaging）和髓鞘新形成——电子显微（electron microscopy）获得确认。从而研究人员提出针对LINGO-1或其途径的对抗治疗是一种治疗中枢神经系统CNS脱髓鞘疾病的新方法。
（生物通：张迪）

原文摘要：
Nature Medicine 13, 1228 - 1233 (2007)
Published online: 30 September 2007 | doi:10.1038/nm1664
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis 『Abstract』

吴武田 教授

姓　　名：吴武田
性　　别：男
职　　称：教授
学　　历：博士研究生
何种导师: 博士生导师
学科专业：人体解剖与组织胚胎学; 神经生物学
研究方向：神经损伤和再生机制的基础研究
行政职务：
E-mail: [e-mail]
电话：[phone](O)


一般简介:

吴武田, 神经科学博士,博士生导师。

1988-1991年，美国Graduate School of Old Domonion University and Eastern Virginia Medical School,神经科学博士；
1992-1996年，美国Eastern Virginia Medical School神经科学系，助理教授；
1996-1997年香港大学解剖系，助理教授；
1997年至今，香港大学医学院解剖学系，副教授。中山大学客座教授。

Journal of Histochem Cyrochem、Brain research、Experimental Neurology和Journal of Comparative Neurology的审稿专家；美国PVA脊髓研究基金委员会、美国Paralysis研究基金会评审专家。

近20年来，吴武田博士一直致力于“神经损伤和再生机制的基础研究”，先后承担美国科研基金5项（其中有NIH基金），香港科研基金8项。发表论文80余篇，被引频次1000余次，直接指导博士生11名，博士后13名。吴武田博士是脊髓损伤研究领域的国际知名学者，曾四次应邀在国际神经科学会议上作：“神经移植、NOS在神经损伤和再生中的作用”的专题报告。并应邀参编著名神经科学丛书：“Handbook of Chemical Neuroanatomy”。还作为分课题负责人承担2003-2008年 国家科技部重大项目基金(973项目)---“神经损伤的修复和重建的应用研究”。

2003年以来主要科研论文如下:
1. Chan, Y.M., Yick, L.W., Yip, H.K., So, K-F, Oppenheim, R.W. and Wu, W.*: Inhibition of caspases promotes long-term survival and reinnervation by axotomized spinal motoneurons of denervated muscle in newborn rats. Experimental Neurology, 181:190-203, 2003. (Wu, W: corresponding author).
2. Wu, W.*, Li, L., Yick, L.W., Chai, H., Xie,Y.Y., Yang, Y., Prevette, D.M. and Oppenheim, R.W.: GDNF and BDNF alter the expression of NOS, c-Jun, and p75 and prevent motoneuron death following spinal root avulsion. J. Neurotrauma, 20:603-612, 2003. (Wu, W: corresponding author).
3. Xie, Y.Y., Yao, Z.B., Chai, H., Wong, W.M. and Wu, W.*: Re-expression and regulation of low-ffinity nerve growth factor receptor (p75) in spinal motor neurons of aged rats following axonal injury. Developmental Neuroscience, 25:71-78, 2003. (Wu, W: corresponding author).
4. Xie, Y.Y., Yao, Z.B., Chai, H., Wong, W.M. and Wu, W.*: Potential roles of Alzheimer precursor protein A4 and b-Amyloid in the survival and function of aged spinal motor neurons following axonal injuries. J. Neuroscience Research, 73:557-564, 2003. (Wu, W: corresponding author).
5. Yaun, Q, Wu, W.*, So, K-F: Inflammatory response of spinal motoneurons to axonal injury in newborn rats. Developmental Neuroscience, 25:65-71, 2003. (Wu, W: corresponding author).
6. Yick, L.W., Cheung, P.T., So, K-F and Wu, W.*: Axonal regeneration of Clarke’s neurons beyond the spinal cord injury scar after treatment with chondroitinase ABC. Experimental Neurology, 182:160-168, 2003. (Wu, W: corresponding author).
7. Gu, H.Y., Chai, H., Zhang, J.Y., Yao, Z.B., Zhou, L.H., Bruce, I. and Wu, W.*: Survival, regeneration and functional recovery of motoneurons in adult rats by reimplantation of ventral root following spinal root avulsion. Europ. J. Neurosci. 19:2123-2131, 2004. (Wu, W., corresponding author).
8. Wu, W.*, Chai, H., Zhang, J.Y., Gu, H.Y., Xie, Y.Y. and Zhou, L.H.: Delayed implantation of a peripheral nerve graft reduces motoneuron survival but does not affect regeneration following spinal root avulsion in adult rats. J. of Neurotrauma, 21(8): 1050-1058, 2004. (Wu, W.., corresponding author).
9. Yick,L.W., So, K-F, Cheung, P.T. and Wu, W.*: Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J. of Neirotrauma, 21(7):932-943, 2004. (Impact:2.866; Citation:2). 50%
10. Gu, H.Y., Chai, H., Zhang, J.Y., Yao, Z.B., Zhou, L.H., Wong, W.M., Bruce, I. and Wu, W.*: Survival, regeneration and functional recovery of motoneurons after delayed reimplantation of ventral root in adult rat. Exp. Neurol. 192:89-99, 2005. (Wu, W., corresponding author).
11. Zeng, Y.S., Ding, Y., Wu, L.Z., Guo, J.S., Li, H.B. and Wu, W.*: Co-transplantation of Schwann cells promotes the survival and differentiation of neural stem cells transplanted into the injured spinal cord. Dev. Neurosci. 27:20-26, 2005. (Wu, W., corresponding author).
12. Chu, T.H. and Wu, W.*: Nitric oxide synthase inhibitor attenuates number of regenerating spinal motoneurons in adult rats. Neuroreport. 17(10):969-73. 2006. (Wu, W., corresponding author).
13. Yang, Y., Xie, Y.Y., Chai, H., Fan, F., Liu, S.H., Liu, H., Bruce, I., and Wu, W.*: Microarray Analysis of Gene Expression Patterns in Adult Spinal Motoneurons after Different types of Axonal Injuries. Brain Res. 1075:1-12, 2006. (Wu, W., corresponding author).
14. Yuan, Q.J., Scott, D.E., So, K.F. and Wu, W.*: Developmental changes of nitric oxide synthase expression in the rat hypothalamo-neurohypophyseal system. Anat. Record. 288A:36-45, 2006. (Wu, W., corresponding author).
15. Yuan, Q.J., Hu, B, So, K.F. and Wu, W.*: Age-related reexpression of p75 in axotomized motoneurons. NeuroReport, 17:711-715, 2006. (Wu, W., corresponding author).
16. Yuan, Q., Scott, D.E., So, K.F. and Wu, W.*: The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats. Brain Res. 1113(1):45-53. 2006. (Wu, W., corresponding author).
17. Zhou, L.H. and Wu, W.*: Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat. Exp. Neurol.197:84-92. 2006. (Wu, W., corresponding author).
18. Zhou, L.H. and Wu, W.*: Survival of injured spinal motoneurons in adult rat upon treatment with glial cell line-derived neurotrophic factor at 2 weeks but not at 4 weeks after root avulsion. J Neurotrauma. 23(6):920-7. 2006. (Wu, W., corresponding author).
19. Guo, J.S., Zeng, Y.S., Liang, Y.X., Wang, L., Su, H.X., Wu, W.*: Cyclosporine affects the proliferation and differentiation of neural stem cells in culture. Neuroreport, 18(9):863-868. 2007. (Wu, W., corresponding author).
20. Su, H., Chu, T.H. and Wu, W.*: Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord. Exp Neurol. 206(2):296-307. 2007. (Wu, W., corresponding author).
21. Yuan, Q., Scott, D.E., So, K.F. and Wu, W.*: Differential Activation of c-fos Immunoreactivity After Hypophysectomy in Developing and Adult Rats. Anat Rec (Hoboken). 290(9):1050-6. 2007. (Wu, W., corresponding author).
22. Yuan, Q., Scott, D.E., So, K.F. and Wu, W.*. A subpopulation of reactive astrocytes at affected neuronal perikarya after hypophysectomy in adult rats. Brain Res. 1159:18-27. 2007. (Wu, W., corresponding author).
23. Zeng, Y.S., Nie, J.H., Zhang, W., Chen, S.J. and Wu, W.*: Morphine acts via µ-opioid receptors to enhance spinal regeneration and synaptic reconstruction of primary afferent fibers injured by sciatic nerve crush. Brain Res, 1113:108-113. 2007. (Wu, W., corresponding author).