Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin
The emergence of myelin marks an evolutionary leap from jawless to jawed vertebrates. Although myelin's role in promoting rapid neural signal transmission and brain complexity is known, its neuroprotective mechanisms in complex signal transmission remain unclear. This study identifies the criti...
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Elsevier
2025-09-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725002769 |
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| author | Yinjie Zhao Zikang Li Weiqun Lu |
| author_facet | Yinjie Zhao Zikang Li Weiqun Lu |
| author_sort | Yinjie Zhao |
| collection | DOAJ |
| description | The emergence of myelin marks an evolutionary leap from jawless to jawed vertebrates. Although myelin's role in promoting rapid neural signal transmission and brain complexity is known, its neuroprotective mechanisms in complex signal transmission remain unclear. This study identifies the critical FoxO gene family member, foxo1a, as essential to the evolution of jawed vertebrates by comparing divergence times and gene family heterogeneity between jawless and jawed vertebrates. We found that foxo1a is located in zebrafish oligodendrocytes and myelin, playing a key antioxidant protective role. Specifically, we found that knocking out the foxo1a gene leads to abnormal myelin development in the central nervous system of zebrafish, a reduction in oligodendrocytes, astrocytes, and myelin markers, and induces freezing behavior. Further research revealed that this is related to oxidative stress responses and ferroptosis in the central nervous system of zebrafish following the deficiency of the foxo1a gene. Mechanistically, we discovered that foxo1a is involved in regulating oxidative stress responses and iron homeostasis in the central nervous system by directly regulating the promoter activity of the slc7a11 gene. In terms of application, we found that exogenous supplementation of foxo1a can exert antioxidant protective effects in a copper sulfate-induced myelin damage model. More importantly, we found a parallelism of the foxo1a-slc7a11 axis in both zebrafish and human cells, suggesting that the foxo1a-slc7a11 axis might be an evolutionarily conserved neural defense strategy in jawed vertebrates. In conclusion, our study elucidates the critical role of foxo1a in maintaining antioxidant homeostasis in the central nervous system and provides new insights into the adaptive evolution of the central nervous system in jawed vertebrates. |
| format | Article |
| id | doaj-art-7c64b7a66f664e74adcf672c050868a1 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-7c64b7a66f664e74adcf672c050868a12025-08-24T05:12:34ZengElsevierRedox Biology2213-23172025-09-018510376310.1016/j.redox.2025.103763Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelinYinjie Zhao0Zikang Li1Weiqun Lu2National Demonstration Center for Experimental Fisheries Science Education (Shanghai Ocean University), Shanghai, 201306, China; International Research Center for Marine Biosciences (Shanghai Ocean University), Ministry of Science and Technology, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, Shanghai, 201306, ChinaNational Demonstration Center for Experimental Fisheries Science Education (Shanghai Ocean University), Shanghai, 201306, China; International Research Center for Marine Biosciences (Shanghai Ocean University), Ministry of Science and Technology, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, Shanghai, 201306, ChinaNational Demonstration Center for Experimental Fisheries Science Education (Shanghai Ocean University), Shanghai, 201306, China; International Research Center for Marine Biosciences (Shanghai Ocean University), Ministry of Science and Technology, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, Shanghai, 201306, China; Corresponding author.National Demonstration Center for Experimental Fisheries Science Education (Shanghai Ocean University), Shanghai, 201306, China.The emergence of myelin marks an evolutionary leap from jawless to jawed vertebrates. Although myelin's role in promoting rapid neural signal transmission and brain complexity is known, its neuroprotective mechanisms in complex signal transmission remain unclear. This study identifies the critical FoxO gene family member, foxo1a, as essential to the evolution of jawed vertebrates by comparing divergence times and gene family heterogeneity between jawless and jawed vertebrates. We found that foxo1a is located in zebrafish oligodendrocytes and myelin, playing a key antioxidant protective role. Specifically, we found that knocking out the foxo1a gene leads to abnormal myelin development in the central nervous system of zebrafish, a reduction in oligodendrocytes, astrocytes, and myelin markers, and induces freezing behavior. Further research revealed that this is related to oxidative stress responses and ferroptosis in the central nervous system of zebrafish following the deficiency of the foxo1a gene. Mechanistically, we discovered that foxo1a is involved in regulating oxidative stress responses and iron homeostasis in the central nervous system by directly regulating the promoter activity of the slc7a11 gene. In terms of application, we found that exogenous supplementation of foxo1a can exert antioxidant protective effects in a copper sulfate-induced myelin damage model. More importantly, we found a parallelism of the foxo1a-slc7a11 axis in both zebrafish and human cells, suggesting that the foxo1a-slc7a11 axis might be an evolutionarily conserved neural defense strategy in jawed vertebrates. In conclusion, our study elucidates the critical role of foxo1a in maintaining antioxidant homeostasis in the central nervous system and provides new insights into the adaptive evolution of the central nervous system in jawed vertebrates.http://www.sciencedirect.com/science/article/pii/S2213231725002769Myelinfoxo1aAntioxidant defenseFerroptosisJawed vertebrates |
| spellingShingle | Yinjie Zhao Zikang Li Weiqun Lu Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin Redox Biology Myelin foxo1a Antioxidant defense Ferroptosis Jawed vertebrates |
| title | Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin |
| title_full | Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin |
| title_fullStr | Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin |
| title_full_unstemmed | Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin |
| title_short | Guardian of myelin and neural Integrity: foxo1a through slc7a11 mitigating oxidative damage in myelin |
| title_sort | guardian of myelin and neural integrity foxo1a through slc7a11 mitigating oxidative damage in myelin |
| topic | Myelin foxo1a Antioxidant defense Ferroptosis Jawed vertebrates |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725002769 |
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