{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T12:18:00Z","timestamp":1778933880852,"version":"3.51.4"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neuroinform."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Autism 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fninf.2025.1563799","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:13:28Z","timestamp":1744348408000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model"],"prefix":"10.3389","volume":"19","author":[{"given":"Guoqiang","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunying","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hafsh","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiachi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruobing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s42003-021-01699-w","article-title":"Deepacson automated segmentation of white matter in 3D electron microscopy","volume":"4","author":"Abdollahzadeh","year":"2021","journal-title":"Commun. 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