中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (3): 366-371.doi: 10.4103/1673-5374.202926

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

神经发炎导致的神经发育失调:神经发育障碍和神经疾病的关键差异

  

  • 收稿日期:2017-03-16 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    本文由NIH(R01NS080844)(LWF),Michael J. Fox基金会(YP),校内研究支援计划(YP)以及美国密西西比大学医学中心儿科新生儿医学基金共同赞助

Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders

Lir-Wan Fan, Yi Pang   

  1. Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders
  • Received:2017-03-16 Online:2017-03-15 Published:2017-03-15
  • Contact: Yi Pang, M.D., Ph.D., ypang@umc.edu.
  • Supported by:

    The authors’ work is supported by grants from NIH (R01NS080844) (LWF), Michael J. Fox foundation (YP), Intramural Research Support Program (YP), and Newborn Medicine Funds from the Department of Pediatrics, University of Mississippi Medical Center.

摘要:

胚胎神经发生由细胞发育的多个步骤组成,包括神经前体细胞增殖,分化,迁移和成熟。这些事件主要由遗传程序控制,但也可能受表观遗传和细胞外因素的影响,这些因素易于产生不利的产前环境障碍。最新数据表明,许多神经发育和/或神经精神障碍,包括ASD,ADHD,SZ,重性抑郁症和双相障碍等,可能源自产前发育期间的异常神经发生。成人神经发生,特别是在SGZ中,是具有高度塑性的,并且可以受到各种生理刺激,如身体运动和行为体验以及非生理刺激,如包括抗抑郁药等某些药物影响。在神经发生增强的情况下,新神经元对功能恢复的贡献是有限的,因为大多数新生神经元(约80%)会因为凋亡而死亡。新生儿神经元存活不佳的确切机制尚未得到完全解读,但可能主要归因于成人脑的本质上和外在的挑战性细胞外环境。
本文依据上述原因表示,成人脑的细胞外环境不利于神经发生,并且可以在疾病期间进一步修饰阻碍神经发生。而神经炎症是脑细胞对旨在维持体内平衡和修复组织病理刺激的复杂细胞和分子反应。由于神经炎症和神经发生改变通常在中枢神经系统疾病中发现,研究神经炎症在失调神经发生中的致病作用已经获得越来越多的关注。神经炎症影响胚胎和成人神经发生,或许是许多神经发育、神经精神病学和神经疾病的发病机制。然而,许多问题仍然没有得到解决。例如,简单地说,在发炎脑中,不同范围的炎症分子共存并潜在地相互作用,并且对神经发生的阻碍作用可能不同于单个细胞因子的阻碍作用。此外,这种效应可以在胚胎和成人脑之间显着变化。当神经炎症在不同疾病的情况下如何调节神经发生的精确机制被更好地阐明时,希望通过靶向神经炎症来调节神经发生,进而可以为那些脑疾病提供新的治疗策略。

ORCID:0000-0003-0453-6921(Yi Pang)

Abstract:

Embryonic neurogenesis is the process of generating neurons, the functional units of the brain. Because of its sensitivity to adverse intrauterine environment such as infection, dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders (ASD). Adult neurogenesis, although is restricted to a few neurogenic niches, plays pivotal roles in brain plasticity and repair. Increasing evidence suggests that impairments in adult neurogenesis are involved in major neurodegenerative disorders such as Alzheimer’s disease. A hallmark feature of these brain disorders is neuroinflammation, which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment. In this review paper, we present evidence from both experimental and human studies to show a complex picture of relationship between these two events, and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neurodevelopmental and neurological disorders.

Key words: microglia, neurodegeneration, autism, embryonic neurogenesis, adult neurogenesis, cytokine, aging