Aoki Shun, Hori Masato, Zhang Hanjie, Tsujioka Hiroshi, Yamashita Toshihide
Department of Molecular Neuroscience, Graduate School of Frontier Biosciences, Osaka University, 2-2, Yamadaoka, Suita, Osaka, Japan.
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, Japan.
Neurochem Res. 2025 Apr 25;50(3):153. doi: 10.1007/s11064-025-04389-9.
In mammals, spinal cord injury often results in permanent impairment of motor function owing to ineffective tissue regeneration. Unlike mammals, zebrafish have the remarkable ability to regenerate many tissues, including the spinal cord. Cross-species comparison is an attractive approach for revealing regeneration-specific mechanisms, but the large evolutionary distance between species sometimes hinders direct comparison. Recent studies have revealed that another model fish species, medaka, has a low regenerative ability in some tissues, making comparisons with them advantageous to revealing regeneration-specific mechanisms. However, their spinal cord regenerative ability has not been compared to other models. In this study, we functionally and histologically compared the spinal cord regeneration abilities of zebrafish and medaka. Swimming speed recovery was significantly lower in medaka than in zebrafish. Bridging of glia and neural tissue were thinner in medaka than in zebrafish. Axonal extension across the injured site was observed in zebrafish but not in medaka. Comparison of their gene expression profiles revealed genes involved in "Regeneration" were upregulated in zebrafish, whereas genes related to "Synaptic signaling" were downregulated in medaka. These results suggest that the ability to regenerate the spinal cord is lower in medaka than in zebrafish, making medaka an attractive model for revealing the mechanisms of spinal cord regeneration.
在哺乳动物中，脊髓损伤往往会因组织再生无效而导致运动功能的永久性损伤。与哺乳动物不同，斑马鱼具有显著的能力来再生包括脊髓在内的许多组织。跨物种比较是揭示再生特异性机制的一种有吸引力的方法，但物种之间巨大的进化距离有时会阻碍直接比较。最近的研究表明，另一种模式鱼类——青鳉，在某些组织中的再生能力较低，这使得与它们进行比较有利于揭示再生特异性机制。然而，它们的脊髓再生能力尚未与其他模型进行比较。在本研究中，我们在功能和组织学上比较了斑马鱼和青鳉的脊髓再生能力。青鳉的游泳速度恢复明显低于斑马鱼。青鳉中神经胶质和神经组织的桥接比斑马鱼更薄。在斑马鱼中观察到轴突穿过损伤部位的延伸，而在青鳉中未观察到。它们基因表达谱的比较显示，参与“再生”的基因在斑马鱼中上调，而与“突触信号传导”相关的基因在青鳉中下调。这些结果表明，青鳉的脊髓再生能力低于斑马鱼，这使得青鳉成为揭示脊髓再生机制的一个有吸引力的模型。
