Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model
IntroductionAutism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders with complex etiologies, including genetic, environmental, and neuroanatomical factors. While the exact mechanisms underlying ASD remain unclear, structural abnormalities in the brain offer valuabl...
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Frontiers Media S.A.
2025-04-01
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| author | Guoqiang Zhao Guoqiang Zhao Ao Cheng Jiahao Shi Jiahao Shi Peiyao Shi Jun Guo Chunying Yin Hafsh Khan Hafsh Khan Jiachi Chen Jiachi Chen Pengcheng Wang Pengcheng Wang Jiao Chen Jiao Chen Ruobing Zhang |
| author_facet | Guoqiang Zhao Guoqiang Zhao Ao Cheng Jiahao Shi Jiahao Shi Peiyao Shi Jun Guo Chunying Yin Hafsh Khan Hafsh Khan Jiachi Chen Jiachi Chen Pengcheng Wang Pengcheng Wang Jiao Chen Jiao Chen Ruobing Zhang |
| author_sort | Guoqiang Zhao |
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| description | IntroductionAutism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders with complex etiologies, including genetic, environmental, and neuroanatomical factors. While the exact mechanisms underlying ASD remain unclear, structural abnormalities in the brain offer valuable insights into its pathophysiology. The corpus callosum, the largest white matter tract in the brain, plays a crucial role in interhemispheric communication, and its structural abnormalities may contribute to ASD-related phenotypes.MethodsTo investigate the ultrastructural alterations in the corpus callosum associated with ASD, we utilized serial scanning electron microscopy (sSEM) in mice. A dataset of the entire sagittal sections of the corpus callosum from wild-type and Shank3B mutant mice was acquired at 4 nm resolution, enabling precise comparisons of myelinated axon properties. Leveraging a fine-tuned EM-SAM model for automated segmentation, we quantitatively analyzed key metrics, including G-ratio, myelin thickness, and axonal density.ResultsIn the corpus callosum of Shank3B autism model mouse, we observed a significant increase in myelinated axon density, accompanied by thinner myelin sheaths compared to wild-type. Additionally, we identified abnormalities in the diameter distribution of myelinated axons and deviations in G-ratio. Notably, these ultrastructural alterations were widespread across the corpus callosum, suggesting a global disruption of myelinated axon integrity.DiscussionThis study provides novel insights into the microstructural abnormalities of the corpus callosum in ASD mouse, supporting the hypothesis that myelination deficits contribute to ASD-related communication impairments between brain hemispheres. However, given the structural focus of this study, further research integrating functional assessments is necessary to establish a direct link between these morphological changes and ASD-related neural dysfunction. |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
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| series | Frontiers in Neuroinformatics |
| spelling | doaj-art-fd4077d5173c46b28e5fe70bc2364adf2025-08-20T02:09:35ZengFrontiers Media S.A.Frontiers in Neuroinformatics1662-51962025-04-011910.3389/fninf.2025.15637991563799Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse modelGuoqiang Zhao0Guoqiang Zhao1Ao Cheng2Jiahao Shi3Jiahao Shi4Peiyao Shi5Jun Guo6Chunying Yin7Hafsh Khan8Hafsh Khan9Jiachi Chen10Jiachi Chen11Pengcheng Wang12Pengcheng Wang13Jiao Chen14Jiao Chen15Ruobing Zhang16School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaSchool of Electronic and Information Engineering, Soochow University, Suzhou, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaHefei Comprehensive National Science Center, Institute of Artificial Intelligence, Hefei, ChinaHefei Comprehensive National Science Center, Institute of Artificial Intelligence, Hefei, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaKey Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, ChinaIntroductionAutism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders with complex etiologies, including genetic, environmental, and neuroanatomical factors. While the exact mechanisms underlying ASD remain unclear, structural abnormalities in the brain offer valuable insights into its pathophysiology. The corpus callosum, the largest white matter tract in the brain, plays a crucial role in interhemispheric communication, and its structural abnormalities may contribute to ASD-related phenotypes.MethodsTo investigate the ultrastructural alterations in the corpus callosum associated with ASD, we utilized serial scanning electron microscopy (sSEM) in mice. A dataset of the entire sagittal sections of the corpus callosum from wild-type and Shank3B mutant mice was acquired at 4 nm resolution, enabling precise comparisons of myelinated axon properties. Leveraging a fine-tuned EM-SAM model for automated segmentation, we quantitatively analyzed key metrics, including G-ratio, myelin thickness, and axonal density.ResultsIn the corpus callosum of Shank3B autism model mouse, we observed a significant increase in myelinated axon density, accompanied by thinner myelin sheaths compared to wild-type. Additionally, we identified abnormalities in the diameter distribution of myelinated axons and deviations in G-ratio. Notably, these ultrastructural alterations were widespread across the corpus callosum, suggesting a global disruption of myelinated axon integrity.DiscussionThis study provides novel insights into the microstructural abnormalities of the corpus callosum in ASD mouse, supporting the hypothesis that myelination deficits contribute to ASD-related communication impairments between brain hemispheres. However, given the structural focus of this study, further research integrating functional assessments is necessary to establish a direct link between these morphological changes and ASD-related neural dysfunction.https://www.frontiersin.org/articles/10.3389/fninf.2025.1563799/fullShank3bautism spectrum disordercorpus callosumserial scanning electron microscopymyelinated axons |
| spellingShingle | Guoqiang Zhao Guoqiang Zhao Ao Cheng Jiahao Shi Jiahao Shi Peiyao Shi Jun Guo Chunying Yin Hafsh Khan Hafsh Khan Jiachi Chen Jiachi Chen Pengcheng Wang Pengcheng Wang Jiao Chen Jiao Chen Ruobing Zhang Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model Frontiers in Neuroinformatics Shank3b autism spectrum disorder corpus callosum serial scanning electron microscopy myelinated axons |
| title | Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model |
| title_full | Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model |
| title_fullStr | Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model |
| title_full_unstemmed | Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model |
| title_short | Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model |
| title_sort | large scale em data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model |
| topic | Shank3b autism spectrum disorder corpus callosum serial scanning electron microscopy myelinated axons |
| url | https://www.frontiersin.org/articles/10.3389/fninf.2025.1563799/full |
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