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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 \u201cRegeneration\u201d were upregulated in zebrafish, whereas genes related to \u201cSynaptic signaling\u201d 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.<\/jats:p>","DOI":"10.1007\/s11064-025-04389-9","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:38:20Z","timestamp":1745541500000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparison of Spinal Cord Regeneration Capacity in Zebrafish and Medaka"],"prefix":"10.1007","volume":"50","author":[{"given":"Shun","family":"Aoki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tsujioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"4389_CR1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1515\/revneuro-2015-0001","volume":"26","author":"M Fakhoury","year":"2015","unstructured":"Fakhoury M (2015) Spinal cord injury: overview of experimental approaches used to restore locomotor activity. 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