{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:04:40Z","timestamp":1785434680742,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,19]]},"group-title":"Neuroscience","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL160102"],"award-info":[{"award-number":["HL160102"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL144454"],"award-info":[{"award-number":["HL144454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL144801"],"award-info":[{"award-number":["HL144801"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL151389"],"award-info":[{"award-number":["HL151389"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL126523"],"award-info":[{"award-number":["HL126523"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NS114097"],"award-info":[{"award-number":["NS114097"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Rett Syndrome Innovation Award"],"award-info":[{"award-number":["Rett Syndrome Innovation Award"]}],"id":[{"id":"https:\/\/ror.org\/00e7vz537","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Rett Syndrome is a rare, x-linked genetic neurological disorder caused by MECP2 gene mutations. This progressive neurodevelopmental disorder hinders patients\u2019 ability to breathe and eat normally. It is unclear how\n                  <jats:italic>Mecp2-<\/jats:italic>\n                  deficiency results in a high percentage of dysphagia and aspiration pneumonia in patients with Rett syndrome. We aim to determine the effects of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  -deficiency on swallow related neuromuscular mechanisms contributing to dysphagia in Rett syndrome. Swallow and breathing were detected using electrophysiology in the submental and laryngeal muscle complexes and the hypoglossal and vagus nerves. Several medullary motoneuron populations involved in swallowing were examined by immunohistochemistry in pre and post symptomatic\n                  <jats:italic>Mecp2<\/jats:italic>\n                  -deficient male and female mice. Swallow-related submental complex duration and amplitude were significantly decreased in both\n                  <jats:italic>Mecp2<\/jats:italic>\n                  -\/y and\n                  <jats:italic>Mecp2<\/jats:italic>\n                  +\/-compared to wild-type, due to decreased motor unit activation. In both\n                  <jats:italic>Mecp2-<\/jats:italic>\n                  deficient mice, cholinergic staining in hypoglossal, facial, and trigeminal nuclei were decreased. We noted a significant increase in the transition time from inspiration to swallow, swallow to the subsequent inspiration, and impaired respiratory rhythm regeneration in\n                  <jats:italic>Mecp2<\/jats:italic>\n                  -\/y, but not\n                  <jats:italic>Mecp2<\/jats:italic>\n                  +\/- mice.\n                <\/jats:p>\n                <jats:p>\n                  <jats:italic>Mecp2-<\/jats:italic>\n                  deficiency resulted in impaired brainstem cholinergic signaling, which contribute to weakened submental muscle complex activity, and impaired swallow related laryngeal vestibular closure. These results suggest\n                  <jats:italic>Mecp2-<\/jats:italic>\n                  deficient mice are a viable pre-clinical model to further study dysphagia in Rett syndrome.\n                <\/jats:p>","DOI":"10.1101\/2025.11.19.689305","type":"posted-content","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:25:14Z","timestamp":1763598314000},"source":"Crossref","is-referenced-by-count":0,"title":["Mecp2 deficiency induces dysphagia in a preclinical model of Rett Syndrome"],"prefix":"10.64898","author":[{"given":"Luiz Marcelo","family":"Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam Saeed","family":"Aslam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Marino","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Huff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025112115450998000_2025.11.19.689305v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1956.19.1.44"},{"key":"2025112115450998000_2025.11.19.689305v1.2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1152\/physiol.00005.2021","article-title":"Deglutition and the regulation of the swallow motor pattern","volume":"38","year":"2023","journal-title":"Physiology"},{"key":"2025112115450998000_2025.11.19.689305v1.3","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.929"},{"key":"2025112115450998000_2025.11.19.689305v1.4","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00406.2002"},{"key":"2025112115450998000_2025.11.19.689305v1.5","unstructured":"Vandaele D , Perlman A , Cassell M . Intrinsic fibre architecture and attachments of the human epiglottis and their contributions to the mechanism of deglutition. 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