英国伦敦帝国理工学院Simone Di Giovanni和Marco Brancaccio共同合作，近期取得重要工作进展。他们研究发现，昼夜节律能调节轴突的再生。相关研究成果2023年11月10日在线发表于《细胞—代谢》杂志上。
据介绍，由于轴突再生受限，神经损伤会导致永久性神经功能障碍。损伤依赖性和非依赖性机制为神经元再生提供了重要的见解，然而，支持再生的共同因素仍然难以捉摸。对与神经元再生能力相关的转录组数据集的比较分析显示，昼夜节律是最显著富集的途径。
研究人员证明了感觉神经元具有内源性时钟，并且在坐骨神经损伤的小鼠模型中，它们的再生能力表现出昼夜振荡。转录组学分析同样显示，与轴突再生和昼夜节律时钟相关的过程在一天中的时间依赖性富集。条件性缺失实验表明，Bmal1是神经元内在昼夜节律再生和靶标再支配所必需的。研究人员还发现，锂在野生型小鼠中增强了神经再生，但在缺乏生物钟的小鼠中没有作用。
总之，这些发现表明分子时钟微调了感觉神经元的再生能力，并提出了影响时钟通路的化合物可以作为神经修复的新方法。
附：英文原文
Title: The circadian clock time tunes axonal regeneration
Author: Francesco De Virgiliis, Franziska Mueller, Ilaria Palmisano, Jessica Sarah Chadwick, Lucia Luengo-Gutierrez, Angela Giarrizzo, Yuyang Yan, Matt Christopher Danzi, Carmen Picon-Muoz, Luming Zhou, Guiping Kong, Elisabeth Serger, Thomas Haynes Hutson, Ines Maldonado-Lasuncion, Yayue Song, Christoph Scheiermann, Marco Brancaccio, Simone Di Giovanni
Issue&Volume: 2023-11-10
Abstract: Nerve injuries cause permanent neurological disability due to limited axonal regeneration.Injury-dependent and -independent mechanisms have provided important insight intoneuronal regeneration, however, common denominators underpinning regeneration remainelusive. A comparative analysis of transcriptomic datasets associated with neuronalregenerative ability revealed circadian rhythms as the most significantly enrichedpathway. Subsequently, we demonstrated that sensory neurons possess an endogenousclock and that their regenerative ability displays diurnal oscillations in a murinemodel of sciatic nerve injury. Consistently, transcriptomic analysis showed a time-of-day-dependentenrichment for processes associated with axonal regeneration and the circadian clock.Conditional deletion experiments demonstrated that Bmal1 is required for neuronalintrinsic circadian regeneration and target re-innervation. Lastly, lithium enhancednerve regeneration in wild-type but not in clock-deficient mice. Together, these findingsdemonstrate that the molecular clock fine-tunes the regenerative ability of sensoryneurons and propose compounds affecting clock pathways as a novel approach to nerverepair.
DOI: 10.1016/j.cmet.2023.10.012
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00381-9
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
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本期文章：《细胞—代谢》：Online/在线发表
