中国科学技术大学胡兵等研究人员合作发现，重编程miR-146b-snphb信号可激活斑马鱼M细胞的轴突线粒体运输，并促进受伤后的轴突再生。该研究于2024年12月8日在线发表于国际学术期刊《神经科学通报》。

研究人员揭示了miR-146b对斑马鱼同源基因syntaphilin b（snphb）表达的抑制作用。通过CRISPR/Cas9和单细胞电穿孔技术，研究人员阐明了miR-146b-snphb轴在Mauthner细胞（M细胞）轴突再生中的积极调控作用，并在全局和单细胞水平上进行了验证。

通过逃逸反应测试，研究人员表明miR-146b-snphb信号通路，积极调节M细胞轴突损伤后的功能恢复。此外，连续动态体内成像显示，重新编程miR-146b显著促进了轴突线粒体，在损伤前和再生早期阶段的运输。

该研究揭示了一条内源性轴突再生调控轴，通过重新编程线粒体运输和锚定促进轴突再生。这一调控涉及非编码RNA和线粒体相关基因，可能为中枢神经系统损伤的修复提供潜在机会。

研究人员表示，急性线粒体损伤和轴突损伤后的能量危机，凸显了线粒体运输作为轴突再生的重要靶点。已知具有强大线粒体锚定作用的Syntaphilin（Snph），已成为线粒体运输和轴突再生的显著抑制因子。因此，研究影响snph基因表达水平的分子机制，可以为调节线粒体运输和增强轴突再生提供可行的策略。

附：英文原文

Title: Reprogramming miR-146b-snphb Signaling Activates Axonal Mitochondrial Transport in the Zebrafish M-cell and Facilitates Axon Regeneration After Injury

Author: Wang, Xin-Liang, Wang, Zong-Yi, Chen, Xing-Han, Cai, Yuan, Hu, Bing

Issue&Volume: 2024-12-08

Abstract: Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.

DOI: 10.1007/s12264-024-01329-5

Source: https://link.springer.com/article/10.1007/s12264-024-01329-5