Regenerative medicine offers hope for patients with diseases of the central and peripheral nervous system. Urodele amphibians such as axolotl display an exceptional regenerative capacity and are considered as essential preclinical model organisms in neurology and regenerative medicine research. Earlier studies have suggested that the limb regeneration ability of this salamander notably decreases with induction of metamorphosis by thyroid hormones. Metamorphic axolotl requires further validation as a negative control in preclinical regenerative medicine research, not to mention the study of molecular substrates of its regenerative abilities. In this study, we report new observations on the effect of experimentally induced metamorphosis on spinal cord regeneration in axolotl. Surprisingly, we found that metamorphic animals were successful to functionally restore the spinal cord after an experimentally induced injury. To discern the molecular signatures of spinal cord regeneration, we performed transcriptomics analyses at 1- and 7-days postinjury (dpi) for both spinal cord injury (SCI)-induced (experimental) and laminectomy (sham) groups. We observed 119 and 989 differentially expressed genes at 1- and 7-dpi, respectively, while the corresponding mouse orthologous genes were enriched in junction-, immune system-, and extracellular matrix-related pathways. Taken together, our findings challenge the prior notions of limited regenerative ability of metamorphic axolotl which exhibited successful spinal cord regeneration in our experience. Moreover, we report on molecular signatures that can potentially explain the mechanistic substrates of the regenerative capacity of the metamorphic axolotl. To the best of our knowledge, this is the first report on molecular responses to SCI and functional restoration in metamorphic axolotls. These new findings advance our understanding of spinal cord regeneration, and may thus help optimize the future use of axolotl as a preclinical model in regenerative medicine and integrative biology fields.

中文翻译：

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脊髓功能恢复的临床前分子特征：优化再生医学中的变形A（Ambystoma mexicanum）模型。

再生医学为患有中枢和周围神经系统疾病的患者提供了希望。诸如rod等两栖类动物具有出色的再生能力，被认为是神经病学和再生医学研究中必不可少的临床前模型生物。较早的研究表明，这种sa​​l的肢体再生能力会因甲状腺激素引起的变态而明显降低。变质x需要在临床前再生医学研究中作为阴性对照进行进一步验证，更不用说对其再生能力的分子底物的研究了。在这项研究中，我们报告了实验诱导的变态对on中脊髓再生的影响的新观察。出奇，我们发现，在实验性损伤后，变态动物成功地恢复了脊髓的功能。为了辨别脊髓再生的分子特征，我们在损伤后第1天和第7天（dpi）对脊髓损伤（SCI）诱导的（实验）和椎板切除术（假手术）组进行了转录组学分析。我们分别在1和7 dpi观察到119和989个差异表达的基因，而相应的小鼠直系同源基因在连接，免疫系统和细胞外基质相关途径中富集。综上所述，我们的发现挑战了先前的观念，即在我们的经验中，变形in的再生能力有限，后者在脊髓再生中表现出成功。此外，我们报告了可以潜在地解释变质a再生能力的机械底物的分子标记。据我们所知，这是关于变态轴突对SCI的分子反应和功能恢复的第一份报告。这些新发现促进了我们对脊髓再生的理解，因此可能有助于优化将x索作为再生医学和整合生物学领域的临床前模型的未来用途。