Department of Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden.
Nat Commun. 2024 May 21;15(1):4331. doi: 10.1038/s41467-024-48729-9.
The adult zebrafish spinal cord displays an impressive innate ability to regenerate after traumatic insults, yet the underlying adaptive cellular mechanisms remain elusive. Here, we show that while the cellular and tissue responses after injury are largely conserved among vertebrates, the large-size fast spinal zebrafish motoneurons are remarkably resilient by remaining viable and functional. We also reveal the dynamic changes in motoneuron glutamatergic input, excitability, and calcium signaling, and we underscore the critical role of calretinin (CR) in binding and buffering the intracellular calcium after injury. Importantly, we demonstrate the presence and the dynamics of a neuron-to-neuron bystander neuroprotective biochemical cooperation mediated through gap junction channels. Our findings support a model in which the intimate and dynamic interplay between glutamate signaling, calcium buffering, gap junction channels, and intercellular cooperation upholds cell survival and promotes the initiation of regeneration.
成年斑马鱼脊髓在受到创伤性损伤后表现出令人印象深刻的内在再生能力，但潜在的适应性细胞机制仍难以捉摸。在这里，我们表明，尽管受伤后的细胞和组织反应在脊椎动物中基本保持一致，但大型快速运动的斑马鱼运动神经元具有惊人的弹性，能够保持存活和功能。我们还揭示了运动神经元谷氨酸能输入、兴奋性和钙信号的动态变化，并强调钙结合蛋白（CR）在受伤后结合和缓冲细胞内钙的关键作用。重要的是，我们证明了通过缝隙连接通道介导的神经元间旁观者神经保护生化合作的存在和动态变化。我们的研究结果支持这样一种模式，即谷氨酸信号、钙缓冲、缝隙连接通道和细胞间合作之间的密切和动态相互作用维持细胞存活并促进再生的启动。
