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bioRxiv · 10.1101/2025.11.19.689305

Mecp2 deficiency induces dysphagia in a preclinical model of Rett Syndrome

Oliveira, L. M. M.·Aslam, M. S.·Ramirez, J. M.·Huff, A.
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Abstract

Rett Syndrome is a rare, x-linked genetic neurological disorder caused by MECP2 gene mutations. This progressive neurodevelopmental disorder hinders patients ability to breathe and eat normally. It is unclear how Mecp2-deficiency results in a high percentage of dysphagia and aspiration pneumonia in patients with Rett syndrome. We aim to determine the effects of Mecp2-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 Mecp2-deficient male and female mice. Swallow-related submental complex duration and amplitude were significantly decreased in both Mecp2-/y and Mecp2+/-compared to wild-type, due to decreased motor unit activation. In both Mecp2-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 Mecp2-/y, but not Mecp2+/- mice. Mecp2-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 Mecp2-deficient mice are a viable pre-clinical model to further study dysphagia in Rett syndrome.

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Oliveira, L. M. M., Aslam, M. S., Ramirez, J. M., Huff, A.. 2025-11-19. Mecp2 deficiency induces dysphagia in a preclinical model of Rett Syndrome. https://doi.org/10.1101/2025.11.19.689305

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