{"paper_id":"b23bd603-8ecb-478c-9dd5-671787f34f3d","body_text":"Tanycyte-mediated synapse pruning shapes hypothalamic circuits controlling metabolism | 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 Tanycyte-mediated synapse pruning shapes hypothalamic circuits controlling metabolism Fanny Langlet, Rafik Dali, Irina Kolotuev, David Lopez-Rodriguez, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8143272/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Synaptic pruning by glial cells is critical for refining neural circuits, yet which glial populations mediate this process in hypothalamic networks controlling energy balance remains poorly understood. Here, using 3D-ultrastructural analyses and molecular approaches, we show that tanycytes —specialized glial cells lining the third ventricle— actively engulf excitatory synapses in the mediobasal hypothalamus during a defined postnatal window. This phagocytic activity relies on tanycytic MFG-E8 and phosphatidylserine exposure on synaptic elements. Disruption of this pathway reduces synapse uptake in vitro and alters body weight control around weaning and glucose homeostasis in adulthood. These findings identify tanycytes as previously unrecognized glial mediators of synaptic pruning in hypothalamic circuits, establishing their active role in shaping neural networks underlying energy balance. Biological sciences/Neuroscience/Development of the nervous system Biological sciences/Neuroscience/Feeding behaviour/Hypothalamus Biological sciences/Neuroscience/Glial biology Synapse pruning Tanycyte Mfge8 Energy balance Hypothalamic circuits Neurodevelopment Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS1Physiology.xlsx Extended Data Table 1 TableS2Methodes.xlsx Extended Data Table 2 Media1cut.avi Extended Data Media 1 Media2.avi Extended Data Media 2 Cite Share Download PDF Status: Posted 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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