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神经递质在重编程神经元的皮质发育和成熟过程中的早期作用。

Early Actions of Neurotransmitters During Cortex Development and Maturation of Reprogrammed Neurons.

作者信息

Ojeda Jorge, Ávila Ariel

机构信息

Developmental Neurobiology Unit, Biomedical Sciences Research Laboratory, Basic Sciences Department, Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, Chile.

出版信息

Front Synaptic Neurosci. 2019 Nov 21;11:33. doi: 10.3389/fnsyn.2019.00033. eCollection 2019.

Abstract

The development of the brain is shaped by a myriad of factors among which neurotransmitters play remarkable roles before and during the formation and maturation of synaptic circuits. Cellular processes such as neurogenesis, morphological development, synaptogenesis and maturation of synapses are temporary and spatially regulated by the local or distal influence of neurotransmitters in the developing cortex. Thus, research on this area has contributed to the understanding of fundamental mechanisms of brain development and to shed light on the etiology of various human neurodevelopmental disorders such as autism and Rett syndrome (RTT), among others. Recently, the field of neuroscience has been shaken by an explosive advance of experimental approaches linked to the use of induced pluripotent stem cells and reprogrammed neurons. This new technology has allowed researchers for the first time to model in the lab the unique events that take place during early human brain development and to explore the mechanisms that cause synaptopathies. In this context, the role of neurotransmitters during early stages of cortex development is beginning to be re-evaluated and a revision of the state of the art has become necessary in a time when new protocols are being worked out to differentiate stem cells into functional neurons. New perspectives on reconsidering the function of neurotransmitters include opportunities for methodological advances, a better understanding of the origin of mental disorders and the potential for development of new treatments.

摘要

大脑的发育受到众多因素的影响,其中神经递质在突触回路形成和成熟之前及期间发挥着显著作用。诸如神经发生、形态发育、突触形成和突触成熟等细胞过程,受到发育中皮质内神经递质的局部或远端影响,在时间和空间上受到调控。因此,该领域的研究有助于理解大脑发育的基本机制,并为揭示各种人类神经发育障碍(如自闭症和雷特综合征(RTT)等)的病因提供线索。最近,神经科学领域因与诱导多能干细胞和重编程神经元使用相关的实验方法的爆炸性进展而受到震动。这项新技术首次使研究人员能够在实验室中模拟人类早期大脑发育过程中发生的独特事件,并探索导致突触病变的机制。在此背景下,神经递质在皮质发育早期阶段的作用开始得到重新评估,在制定将干细胞分化为功能性神经元的新方案之际,对现有技术水平进行修订变得必要。重新审视神经递质功能的新观点包括方法学进步的机会、对精神障碍起源的更好理解以及新治疗方法开发的潜力。

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