de Chevigny Antoine, Lledo Pierre-Marie
Institut Pasteur, Laboratoire Perception et mémoire, CNRS URA 2182, 25, rue du Docteur-Roux, 75724 Paris Cedex 15, France.
Med Sci (Paris). 2006 Jun-Jul;22(6-7):607-13. doi: 10.1051/medsci/20062267607.
Contrary to the long-held dogma according to which the adult mammalian brain does not produce neurons anymore, neuronal turnover has been reported in two discrete areas of the adult brain: the hippocampus and the olfactory bulb. Adult-generated neurons are produced from neural stem cells located in the hippocampal subgranular zone and the subventricular zone of the lateral ventricles. Recently, number of genetic and epigenetic factors that modulate proliferation of stem cells, migration, differentiation and survival of newborn neurons have been characterized. We know that neurogenesis increases in the diseased brain, after stroke or after traumatic brain injury. Importantly, progenitors from the subventricular zone, but not from the subgranular zone, are incorporated at the sites of injury, where they replace some of the degenerated neurons. Thus, the central nervous system has the capacity to regenerate itself after injury and, today, researchers develop strategies aimed at promoting neurogenesis in diseased areas. This basic research is attracting a lot of attention because of the hope that it will lead to regeneration and reconstruction therapy for the damaged brain. In this review, we discuss major findings concerning the organization of the neurogenic niche located in the subventricular zone and examine both intrinsic and extrinsic factors that regulate adult neurogenesis. Then, we present evidences for the intrinsic capability of the adult brain for cell replacement, and shed light on recent works demonstrating that one can greatly enhance appropriate brain cell replacement by using molecular cues known to endogenously control proliferation, migration, differentiation and/or survival of subventricular zone progenitors. Finally, we review some of the advantages and limits of strategies aimed at using endogenous progenitors and their relevance to human clinics.
与长期以来认为成年哺乳动物大脑不再产生神经元的教条相反，在成年大脑的两个离散区域已报道有神经元更替现象：海马体和嗅球。成年产生的神经元由位于海马体颗粒下区和侧脑室室下区的神经干细胞产生。最近，已鉴定出一些调节干细胞增殖、新生神经元迁移、分化和存活的遗传和表观遗传因素。我们知道，在患病大脑、中风后或创伤性脑损伤后，神经发生会增加。重要的是，来自室下区而非颗粒下区的祖细胞会整合到损伤部位，在那里它们替代一些退化的神经元。因此，中枢神经系统在损伤后具有自我再生的能力，如今，研究人员正在开发旨在促进患病区域神经发生的策略。这项基础研究正吸引着大量关注，因为人们希望它能带来受损大脑的再生和重建治疗。在这篇综述中，我们讨论了有关位于室下区的神经发生微环境组织的主要发现，并研究了调节成年神经发生的内在和外在因素。然后，我们展示了成年大脑进行细胞替代的内在能力的证据，并阐明了最近的研究工作，这些研究表明，通过使用已知可内源性控制室下区祖细胞增殖、迁移、分化和/或存活的分子线索，可以大大增强适当的脑细胞替代。最后，我们回顾了旨在利用内源性祖细胞的策略的一些优点和局限性及其与人类临床的相关性。
