Atkinson-Leadbeater Karen, Hehr Carrie L, Johnston Jill, Bertolesi Gabriel, McFarlane Sarah
Department of Psychology, Mount Royal University, Calgary, Alberta.
Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta.
Dev Dyn. 2016 Jun;245(6):667-77. doi: 10.1002/dvdy.24406. Epub 2016 Apr 21.
Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain.
EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid-diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior.
We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667-677, 2016. © 2016 Wiley Periodicals, Inc.
抗氧化剂，如绿茶多酚表没食子儿茶素没食子酸酯（EGCG），在成熟神经系统的多种条件下具有神经保护作用；然而，它们在发育中的神经系统中的影响很少被探究，在发育中的神经系统中，一个关键步骤是神经元之间连接的形成。轴突从新形成的神经元中伸出，并由其顶端一种称为生长锥的动态结构引导。在这里，我们探究了EGCG对视网膜神经节细胞（RGC）轴突发育的影响，RGC轴突将眼睛与大脑相连。
EGCG直接作用于RGC轴突，在体外和体内均可增加生长锥丝状伪足的数量，丝状伪足是对外部信号作出反应的指状突起。此外，暴露于EGCG会导致RGC轴突引导生长出现严重缺陷，轴突在中脑间脑无法做出到达目标所需的关键转向。有趣的是，在RGC没有显示方向变化的引导点处，EGCG对RGC轴突行为没有影响。
我们提出，EGCG稳定丝状伪足，并阻止轴突在引导决策点改变生长方向所需的正常丝状伪足动态变化。《发育动力学》245:667 - 677，2016年。© 2016威利期刊公司。
