中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 219-225.doi: 10.4103/1673-5374.344837

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

成年斑马鱼视神经损伤诱导的再生伴随着线粒体动力学的时空变化

  

  • 出版日期:2023-01-15 发布日期:2022-06-17
  • 基金资助:

    这项工作得到了鲁汶大学研究委员会(C14/18/053)和佛兰德斯研究基金会(FWO)(G082221N);欧莱雅/联合国教科文组织(为科学界的女性)的个人研究金支持

Optic nerve injury-induced regeneration in the adult zebrafish is accompanied by spatiotemporal changes in mitochondrial dynamics

An Beckers1, Luca Masin1, Annelies Van Dyck1, Steven Bergmans1, Sophie Vanhunsel1, Anyi Zhang1, Tine Verreet2, Fabienne E. Poulain2, Karl Farrow3, 4, 5, Lieve Moons1, 4, *   

  1. 1Neural Circuit Development and Regeneration Research Group, Animal Physiology and Neurobiology Section, Department of Biology, Katholieke Universiteit Leuven, Leuven, Belgium; 2Poulain Lab, Department of Biological Sciences, University of South Carolina, Columbia, SC, USA; 3Neuro-Electronics Research Flanders, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium; 4Leuven Brain Institute, Leuven, Belgium; 5Imec, Leuven, Belgium
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Lieve Moons, PhD, lieve.moons@kuleuven.be,
  • Supported by:
    This work was financially supported by the Katholieke Universiteit Leuven Research Council (C14/18/053) and the research foundation Flanders (FWO) (G082221N). AB holds a personal L’Oréal/UNESCO (For Women in Science) fellowship. LM, AVD, SB, and SV hold a personal FWO fellowship.

摘要:

中枢神经系统轴突再生是一个高能耗过程。与哺乳动物相比,成年斑马鱼神经元损伤后具备恢复功能;相应地,斑马鱼是如何应对这种高能量需求的呢?作者既往表明,成年斑马鱼视神经挤压后,存在拮抗的轴突-树突相互作用,其中 RGC 树突的回缩是有效轴突修复的先决条件。假设“再生树突”范式可能与神经元内线粒体重排有关,因为神经节细胞可能没有足够的资源来同时维持树突和恢复轴突。实验描述了再生过程中不同神经节细胞区室(树突、胞体和轴突)内的线粒体分布和线粒体动力学。视神经挤压导致树突回缩期间树突中的线粒体减少,随后在轴突再生期间视神经/束中出现线粒体增大。视网膜神经元树突再生后,视网膜树突内的线粒体密度恢复到基线水平。此外,在视神经损伤后,在视网膜神经节细胞胞体中观察到线粒体分裂和生物合成的短暂增加。以上研究结果表明,在视神经损伤诱导的再生过程中,线粒体从树突转移到轴突并再次返回,暂时的线粒体动力学变化支持视神经挤压后轴突和树突的依次再生。

https://orcid.org/0000-0003-0186-1411 (Lieve Moons)

Abstract: Axonal regeneration in the central nervous system is an energy-intensive process. In contrast to mammals, adult zebrafish can functionally recover from neuronal injury. This raises the question of how zebrafish can cope with this high energy demand. We previously showed that in adult zebrafish, subjected to an optic nerve crush, an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair. We postulate a ‘dendrites for regeneration’ paradigm that might be linked to intraneuronal mitochondrial reshuffling, as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously. Here, we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments (dendrites, somas, and axons) during the regenerative process. Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction, whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth. Upon dendritic regrowth in the retina, mitochondrial density inside the retinal dendrites returned to baseline levels. Moreover, a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage. Taken together, these findings suggest that during optic nerve injury-induced regeneration, mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush. 

Key words: axonal regeneration, central nervous system, dendrite remodeling, energy metabolism, fission, mitochondria, mitochondrial trafficking, optic nerve crush, retina, zebrafish