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成年海马体中新神经元的形成与整合。

Formation and integration of new neurons in the adult hippocampus.

作者信息

Denoth-Lippuner Annina, Jessberger Sebastian

机构信息

Laboratory of Neural Plasticity, Brain Research Institute, Faculty of Medicine and Faculty of Science, University of Zurich, Zurich, Switzerland.

出版信息

Nat Rev Neurosci. 2021 Apr;22(4):223-236. doi: 10.1038/s41583-021-00433-z. Epub 2021 Feb 25.

Abstract

Neural stem cells (NSCs) generate new neurons throughout life in the mammalian brain. Adult-born neurons shape brain function, and endogenous NSCs could potentially be harnessed for brain repair. In this Review, focused on hippocampal neurogenesis in rodents, we highlight recent advances in the field based on novel technologies (including single-cell RNA sequencing, intravital imaging and functional observation of newborn cells in behaving mice) and characterize the distinct developmental steps from stem cell activation to the integration of newborn neurons into pre-existing circuits. Further, we review current knowledge of how levels of neurogenesis are regulated, discuss findings regarding survival and maturation of adult-born cells and describe how newborn neurons affect brain function. The evidence arguing for (and against) lifelong neurogenesis in the human hippocampus is briefly summarized. Finally, we provide an outlook of what is needed to improve our understanding of the mechanisms and functional consequences of adult neurogenesis and how the field may move towards more translational relevance in the context of acute and chronic neural injury and stem cell-based brain repair.

摘要

神经干细胞(NSCs)在哺乳动物大脑中终生生成新的神经元。成年后生成的神经元塑造大脑功能,内源性神经干细胞有可能被用于脑修复。在本综述中,聚焦于啮齿动物海马体神经发生,我们基于新技术(包括单细胞RNA测序、活体成像以及对行为小鼠中新生细胞的功能观察)突出该领域的最新进展,并描述从干细胞激活到新生神经元整合到现有神经回路的不同发育阶段。此外,我们回顾了目前关于神经发生水平如何被调节的知识,讨论了关于成年后生成细胞存活和成熟的研究结果,并描述了新生神经元如何影响大脑功能。简要总结了支持(和反对)人类海马体终生神经发生的证据。最后,我们展望了为提高我们对成年神经发生机制和功能后果的理解需要做些什么,以及该领域如何在急性和慢性神经损伤以及基于干细胞的脑修复背景下朝着更具转化相关性的方向发展。

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