近日，华东师范大学田阳团队实现了通过比率荧光成像点亮神经分化中的精氨酸代谢动力学。相关论文于2025年9月15日发表在《美国化学会志》上。

精氨酸（Arg）是中枢神经系统中非常重要的氨基酸，在神经干细胞（NSCs）的分化过程中起着关键作用。然而，具体和定量跟踪原地氩动力学提出了重大挑战。

研究组开发了一系列基于苯基活化酯和伯胺之间的亲核取代反应的Arg探针（Rap1-9）。其中，优化后的NIR发射比荧光探针Rap-9在其活性位点表现出最明显的亲电性，可以在体外和体内快速特异性检测Arg。值得注意的是，Rap-9成功地用于O₂^·-刺激的NSC分化过程中Arg动态的实时成像。进一步的研究表明，Arg介导的mTORC1通路的激活可以通过调节线粒体糖酵解到线粒体氧化磷酸化的能量代谢来协调qNSC的再激活和神经元分化。这些发现不仅增强了他们对控制NSC分化的代谢途径的理解，而且为神经科学研究和潜在的治疗干预提供了新的视角。

附：英文原文

Title: Lighting Up Arginine Metabolism Dynamics in Neural Differentiation through Ratiometric Fluorescence Imaging

Author: Jin Yan, Yuxiao Mei, Yudan Zhao, Yang Tian

Issue&Volume: September 15, 2025

Abstract: Arginine (Arg) is a critically important amino acid in the central nervous system and plays a pivotal role in the differentiation of neural stem cells (NSCs). However, specifically and quantitatively tracking Arg dynamics in situ presents a significant challenge. Herein, we developed a series of Arg probes (Rap1–9) based on the nucleophilic substitution reaction between a phenyl-activated ester and a primary amine. Among these, the optimized NIR-emission ratiometric fluorescent probe Rap-9 demonstrated the most pronounced electrophilicity at its reactive site, enabling rapid and specific detection of Arg both in vitro and in vivo. Notably, Rap-9 was successfully utilized for real-time imaging of Arg dynamics during O2·–-stimulated NSC differentiation. Further studies revealed that Arg-mediated activation of the mTORC1 pathway could coordinate qNSC reactivation and neuronal differentiation by regulating mitochondrial energy metabolism from glycolysis to mitochondrial oxidative phosphorylation. These findings not only enhanced our understanding of the metabolic pathways governing NSC differentiation but also offered new perspectives for neuroscience research and potential therapeutic interventions.

DOI: 10.1021/jacs.5c05685

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c05685