Platel Jean-Claude, Stamboulian Séverine, Nguyen Ivy, Bordey Angélique
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520-8082, USA.
Brain Res Rev. 2010 May;63(1-2):60-71. doi: 10.1016/j.brainresrev.2010.02.004. Epub 2010 Feb 24.
Like the liver or other peripheral organs, two regions of the adult brain possess the ability of self-renewal through a process called neurogenesis. This raises tremendous hope for repairing the damaged brain, and it has stimulated research on identifying signals controlling neurogenesis. Neurogenesis involves several stages from fate determination to synaptic integration via proliferation, migration, and maturation. While fate determination primarily depends on a genetic signature, other stages are controlled by the interplay between genes and microenvironmental signals. Here, we propose that neurotransmitters are master regulators of the different stages of neurogenesis. In favor of this idea, a description of selective neurotransmitter signaling and their functions in the largest neurogenic zone, the subventricular zone (SVZ), is provided. In particular, we emphasize the interactions between neuroblasts and astrocyte-like cells that release gamma-aminobutyric acid (GABA) and glutamate, respectively. However, we also raise several limitations to our knowledge on neurotransmitters in neurogenesis. The function of neurotransmitters in vivo remains largely unexplored. Neurotransmitter signaling has been viewed as uniform, which dramatically contrasts with the cellular and molecular mosaic nature of the SVZ. How neurotransmitters are integrated with other well-conserved molecules, such as sonic hedgehog, is poorly understood. In an effort to reconcile these differences, we discuss how specificity of neurotransmitter functions can be provided through their multitude of receptors and intracellular pathways in different cell types and their possible interactions with sonic hedgehog.
与肝脏或其他外周器官一样，成人大脑的两个区域具有通过一种称为神经发生的过程进行自我更新的能力。这为修复受损大脑带来了巨大希望，并激发了对识别控制神经发生信号的研究。神经发生涉及从命运决定到通过增殖、迁移和成熟进行突触整合的几个阶段。虽然命运决定主要取决于遗传特征，但其他阶段则由基因与微环境信号之间的相互作用控制。在此，我们提出神经递质是神经发生不同阶段的主要调节因子。支持这一观点的是，本文描述了选择性神经递质信号及其在最大的神经发生区域——脑室下区（SVZ）中的功能。特别是，我们强调了分别释放γ-氨基丁酸（GABA）和谷氨酸的神经母细胞与星形胶质细胞样细胞之间的相互作用。然而，我们也提出了目前我们对神经发生中神经递质的认识存在的几个局限性。神经递质在体内的功能在很大程度上仍未被探索。神经递质信号一直被视为是统一的，这与SVZ的细胞和分子镶嵌性质形成了鲜明对比。神经递质如何与其他保守分子（如音猬因子）整合，目前还知之甚少。为了调和这些差异，我们讨论了如何通过神经递质在不同细胞类型中的众多受体和细胞内途径及其与音猬因子可能的相互作用来提供神经递质功能的特异性。
