Focal-White Matter Lesions Stimulate Circuit Wide Myelinogenesis to Facilitate Myelin Repair

Focal-White Matter Lesions Stimulate Circuit Wide Myelinogenesis to Facilitate Myelin Repair | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Focal-White Matter Lesions Stimulate Circuit Wide Myelinogenesis to Facilitate Myelin Repair Feng Mei, Zhi-Yu Liu, Ming-Chen Liu, De-Cai Tian, Qijing Lei, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9054740/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Focal demyelination results in conduction block along neural circuits, leading to functional deficits in diseases such as multiple sclerosis (MS). As demyelination disrupts circuit function, could oligodendroglia in non-lesioned regions compensate for circuit dysfunction and contribute to lesion repair? To address this possibility, lysolecithin-induced demyelination in the corpus callosum was performed concomitantly with neuron-specific AAV labeling and cell-lineage tracing of new myelin. We demonstrate non-lesioned regions of the contralateral and ipsilateral cortex display enhanced myelinogenesis, preceding lesion remyelination. By labeling nascent and pre-existing myelin using dual-inducible reporters, we find that myelinogenesis is significantly enhanced in the ipsilateral non-lesioned cortex and corpus callosum, without alteration to pre-existing myelin. Selectively ablating the newly formed oligodendrocytes outside of the lesion impairs remyelination, while enhancing myelination in non-lesioned regions accelerates lesion repair. Collectively, our results establish that focal lesions induce compensatory myelinogenesis to promote remyelination, highlighting the therapeutic potential of early pro-myelinating interventions. Health sciences/Diseases/Neurological disorders/Multiple sclerosis Biological sciences/Neuroscience/Glial biology/Oligodendrocyte Full Text Additional Declarations There is NO Competing Interest. Supplementary Files EXTENDEDDATAFIGURES36.pdf Supplementary Figures 1-5 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9054740","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":609102349,"identity":"ac3f4b89-3a3e-4b74-9e06-c24282a7c244","order_by":0,"name":"Feng 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