{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:02:46Z","timestamp":1782280966352,"version":"3.54.5"},"posted":{"date-parts":[[2023,2,3]]},"group-title":"Neuroscience","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Health","award":["1R01HD092396"],"award-info":[{"award-number":["1R01HD092396"]}]},{"name":"Association Fran\u00e7aise du Syndrome de Rett"},{"name":"Fondation J\u00e9r\u00f4me Lejeune"},{"name":"Initiative d'Excellence d'Aix-Marseille Universit\u00e9 - A*MIDEX","award":["AMX-19-IET-007"],"award-info":[{"award-number":["AMX-19-IET-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in\n                  <jats:italic>MECP2<\/jats:italic>\n                  . Elevated circulating levels of the adipocyte hormone leptin are consistently observed in patients and in mouse models, yet their contribution to disease progression has remained unclear. Here, we show that reducing leptin signaling\u2014either pharmacologically or genetically\u2014 significantly alleviates RTT-like phenotypes in\n                  <jats:italic>Mecp2<\/jats:italic>\n                  -deficient mice. In males, these interventions preserved general health, prevented weight loss, and improved breathing and locomotor functions. At the neuronal level, they restored excitatory\/inhibitory balance in the hippocampus and somatosensory cortex and rescued hippocampal synaptic plasticity. In females, delaying the pathological rise of leptin levels postponed symptom progression. These findings uncover leptin as a key contributor to RTT pathophysiology and position leptin-targeted interventions as a promising therapeutic strategy for this currently untreatable disorder.\n                <\/jats:p>","DOI":"10.1101\/2023.02.03.526251","type":"posted-content","created":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T03:30:18Z","timestamp":1675481418000},"source":"Crossref","is-referenced-by-count":3,"title":["Leptin antagonism improves Rett syndrome phenotype in symptomatic\n                  <i>Mecp2-<\/i>\n                  deficient mice"],"prefix":"10.64898","author":[{"given":"Yasmine","family":"Bela\u00efdouni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diabe","family":"Diabira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Salin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Brosset-Heckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Valsamides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Graziano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7419-6427","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Menuet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary 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