Optic nerve injury-induced regeneration in the adult zebrafish is accompanied by spatiotemporal changes in mitochondrial dynamics.-猫眼课题宝

DOI：

10.4103/1673-5374.344837

发表时间：

2023-01

期刊：

Neural regeneration research

影响因子：

6.1

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Beckers A;Masin L;Van Dyck A;Bergmans S;Vanhunsel S;Zhang A;Verreet T;Poulain FE;Farrow K;Moons L

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241429/

中枢神经系统的轴突再生是一个能量密集型的过程。与哺乳动物相比，成年斑马鱼可以从神经元损伤中恢复功能。这就提出了一个问题，即斑马鱼如何科普这种高能量需求。我们以前表明，在成年斑马鱼，视神经挤压，拮抗轴突树突的相互作用存在，其中视网膜神经节细胞树突的回缩是有效的轴突修复的先决条件。我们假设“轴突再生”范式可能与神经元内线粒体改组有关，因为神经节细胞可能没有足够的资源来同时维持轴突和恢复轴突。在这里，我们的特点是线粒体分布和线粒体动力学在不同的神经节细胞舱（树突，胞体，轴突）在再生过程中。视神经挤压导致树突内线粒体减少，随后轴突再生过程中视神经/视束内线粒体增大。在视网膜中的树突再生后，视网膜树突内的线粒体密度恢复到基线水平。此外，在视神经损伤后的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。两者合计，这些研究结果表明，在视神经损伤诱导的再生，线粒体从树突转移到轴突和回来，线粒体动力学的暂时变化支持视神经挤压后轴突和树突再生。

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.