中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 886-889.doi: 10.4103/1673-5374.184451

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

少突胶质细胞消融是研究脱髓鞘疾病的有效工具

  

  • 出版日期:2016-06-30 发布日期:2016-06-30
  • 基金资助:

    这项工作部分由Genentech支持。

Oligodendrocyte ablation as a tool to study demyelinating diseases

Ahdeah Pajoohesh-Ganji, Robert H. Miller*   

  1. Department of Anatomy and Regenerative Biology, The George Washington University, School of Medicine and Health Sciences, Washington DC, USA
  • Online:2016-06-30 Published:2016-06-30
  • Contact: Robert H. Miller, Ph.D., rhm3@gwu.edu.
  • Supported by:

    This work has been supported in part by Genentech.

摘要:

多发性硬化是影响整个中枢神经系统的一种自身免疫性介导的神经退行性疾病,其特征表现为脱髓鞘和在多个焦点位点上的少突胶质细胞损失。其中多发性硬化患者中第一个也是最常见的临床表现为视神经炎。虽然我们对少突胶质细胞谱系在髓鞘形成和脱髓鞘中的生物学理解是相当充实的,但我们在脱髓鞘对神经元群体造成何种影响方面的研究却很有限。文中指出视网膜神经节细胞凋亡可以在多发性硬化症和视神经炎动物模型中被观察到,并与视神经炎症相关。虽然来自Jimpy小鼠的研究表明视神经的轴突髓鞘有缺失,但视动反射测量显示视觉系统仍保留功能性,这表明视网膜神经节细胞轴突缺乏髓鞘形成对视网膜功能几乎没有影响。脱髓鞘后是否也可以观察到类似的功能保留在以前是未知的,现在可以用少突胶质细胞耗尽方法在MBP-iCP9转基因小鼠的视神经中得到解决。可能的结论是脱髓鞘将导致视网膜神经节细胞凋亡和轴突变性或见于视神经炎的轴突变性,这反映出了炎症因子和非少突胶质细胞凋亡以及直接脱髓鞘。不管得到何种结果,开发新模型,并有选择地消融脊椎动物中枢神经系统的髓鞘细胞会给髓鞘生物学和脱髓鞘病理学见解带来重要启示。

Abstract:

Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.

Key words: multiple sclerosis, oligodendrocyte, apoptosis, demyelination, optic neuritis