中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 878-881.doi: 10.4103/1673-5374.184449

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

在成年小鼠中发现黑质多巴胺神经发生

  

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

    与莫里森实验室成人多巴胺神经发生相关的研究工作是由博伊西州立大学,博伊西州立大学生物分子研究中心和博伊西退伍军人医疗中心,爱达荷州博伊西市支持。以及美国国立卫生研究院医学科学赠款#P20GM103408和P20GM109095研究所机构发展奖提供本科生实习支持。

Discovery of nigral dopaminergic neurogenesis in adult mice

Brad E. Morrison*   

  1. Department of Biological Sciences, Boise State University, Boise, ID, USA; Biomolecular Ph.D. Program, Boise State University, Boise, ID, USA
  • Online:2016-06-30 Published:2016-06-30
  • Contact: Brad E. Morrison, Ph.D., bradmorrison@boisestate.edu
  • Supported by:

    Work involving adult DA neurogenesis in the Morrison lab was supported by resources from Boise State University, The Biomolecular Research Center at Boise State University, and the Boise VA Medical Center, Boise, ID. Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grants #P20GM103408 and P20GM109095 provided undergraduate student internship support.

摘要:

位于中脑黑质区域的多巴胺神经元通过基底节活性是运动控制的调节剂。这些神经元的渐进性丧失是帕金森病最常见的运动障碍标志。驱动帕金森病发病的细胞和分子机制尚未得到很好地理解,因此,目前只有针对症状的治疗方法却无法解决疾病中的神经退变。目前围绕这一概念得到的理论之一是,在黑质区域的多巴胺神经元不能在成年哺乳动物中得到补充,并在帕金森病相关的疾病中观察到成熟神经元死亡。因此,关于成熟神经元的神经变性主要机制,研究主要集中在毒物和/或营养因子撤回方面。然而,确定多巴胺能神经元是否在我们一生中自然产生(即,神经发生)是了解这些细胞的死亡以及得到潜在治疗方法的根本。成人神经发生已经报道可发生在海马神经元、嗅球神经元和纹状体中间神经元等小种群中。这些发现推进了对黑质多巴胺神经元的探索过程。直到最近,研究成人神经发生证据缺乏主要由于无法复制利于多巴胺神经元神经发生的少数研究。这很可能与用于细胞谱系追踪流行方法相关的技术限制。为了克服这些限制,美国博伊西州立大学生物科学系的研究小组设计了一种新颖的谱系追踪方法,为多巴胺神经元成年神经发生提供了令人信服的证据。本文将侧重于研究我们最近的发现和使用的模型。 

orcid: 0000-0002-6356-7149 (Brad E. Morrison) 

Abstract:

Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra. As a result, intensive efforts have focused upon mechanisms that facilitate the death of mature dopaminergic neurons. Unfortunately, these efforts have been unsuccessful in providing an effective treatment to address neurodegeneration in this disease. Therefore, alternative theories of pathogenesis are being explored. Adult neurogenesis of dopaminergic neurons is an attractive concept that would provide a possible mechanism of neurodegeneration as well as offer an endogenous means to replenish affected neurons. To determine whether dopaminergic neurons experience neurogenesis in adult mice we developed a novel cell lineage tracing model that permitted detection of neurogenesis without many of the issues associated with popular techniques. Remarkably, we discovered that dopaminergic neurons are replenished in adult mice by Nestin+/Sox2- progenitor cells. What’s more, the rate of neurogenesis is similar to the rate of dopaminergic neuron loss reported using a chronic, systemic inflammatory response mouse model. This observation may indicate that neuron loss in Parkinson’s disease results from inhibition of neurogenesis.

Key words: Parkinson’s disease, adult neurogenesis, dopaminergic neurons, stem cells, nestin