Received 2003-01-15

Accepted 2003-03-02

The studies of the author mentioned in the review were supported by two R01 grants from the NIH (DA10355 and MH61469 to J.Q.W.), a Dr. Phillip S. Astrowe Trust Award (J.Q.W.) and a grant from the American Heart Association (L.M.).

Corresponding author. Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes St., Rm. M3-225, Kansas City, Missouri 64108, USA, Tel: 816-235-1786; Fax: 816-235-1776; E-mail: wangjq@umkc.edu

Brief Review

Adult neural stem/progenitor cells in neurodegenerative repair

Limin MAO, John Q. WANG*

Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes St., Rm. M3-225, Kansas City, Missouri 64108, USA

Abstract: Although the mammalian brain has long been thought to be entirely postmitotic, the recent discovery has confirmed an existence of neural stem or progenitor cells in various regions of the adult mammalian brain. Like embryonic stem cells, adult neural progenitor cells possess the capacity of self-renewal and differentiation potential for neurogenesis or gliogenesis. In addition to the subventricular zone and hippocampus where active cell division naturally occurs, adult neural progenitors with neurogenic potential exist in the striatum and the vicinity of dopaminergic neurons in the substantia nigra. Normally, progenitors in those regions proliferate at a low level, and most proliferated cells remain uncommitted. In response to the selective lesion of nigrostriatal dopaminergic pathway by the neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine, progenitors in the injured areas markedly increase their proliferation rate. Depending upon the magnitude and kinetics of the lesion, neurogenesis and gliogenesis were induced in the lesion sites at varying extents. A large number of growth and neurotrophic factors influence proliferation and/or differentiation of progenitor cells under normal and lesioned conditions. Some factors (epidermal and basic fibroblast growth factors and brain-derived neurotrophic factor) are facilitatory, while others (usually bone morphogenetic proteins) are inhibitory, for controlling division and fate of neuronal or glial progenitors. Expression of endogenous factors and their respective receptors in existing and newborn cells are also subject to be altered by the lesion. These genomic responses are considered to be important elements for the formation of a local molecular niche for a given phenotypic cell regeneration. Taken together, adult neural progenitor cells in the nigrostriatal dopaminergic system have the ability to respond to the lesion to repopulate missing cells. The regenerative neuro- or gliogenesis in situ can, at least in part, endogenously compensate injured neural elements, and achieve a self-repair of neurodegenerative disorders such as Parkinson′s disease.

Key words: stem cells; striatum; nigra; neurogenesis; cytogenesis; dopamine; parkinson′s disease

成体神经干（前体）细胞在中枢神经系统退行性病变中的修复作用

毛利民, 王强*

密苏里大学药理学教研室， 美国

摘要: 尽管传统概念长期认为成体哺乳动物中枢神经系统缺乏再生增殖能力， 但近年来发现, 在成体若干脑区内确实存在具有再生与分化能力的神经干或神经前体细胞。 这些干细胞在正常情况下仅表现较低的再生分化活动。 不过， 在神经退行性病变中，病灶区内的干细胞可被动员、激活， 并以较高的速率分裂分化以及取代坏死的神经元或胶质细胞，达到自身原位修复的作用。许多神经生长和营养因子具有增强或抑制干细胞分裂和/或分化的能力, 在神经退行性病变中，病灶区内外成熟或新生细胞即可通过表达这些因子， 有效调节干细胞的活动和干细胞主导的修复过程。 总之， 成体神经干细胞可以积极参与急性或慢性神经组织损伤的修复， 通过再生来提供新的神经元以及其他必需的细胞, 以促进功能的恢复。

关键词: 神经干细胞; 纹状体; 黑质； 神经元再生； 细胞再生； 多巴胺； 帕金森氏病

中图分类号: Q426