Original Research ARTICLE
Persistent expression of Serotonin Receptor 5b alters Breathing Behavior in a Mouse model of Rett Syndrome
- 1DFG-Research Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Universitätsmedizin Göttingen, Germany
- 2Institute of Neuro- and Sensory Physiology, Universitätsmedizin Göttingen, Germany
- 3Clinic for Anesthesiology, Universitätsmedizin Göttingen, Germany
Mutations in the transcription factor methyl-CpG-binding protein 2 (MeCP2) cause a delayed neurodevelopmental disorder known as Rett syndrome (RTT). Among many other neurological problems RTT patients show irregular breathing with recurrent apneas or breath-holdings. Mecp2–deficient mice, which recapitulate this breathing phenotype, show a dysregulated expression of G-protein-coupled serotonin receptor 5-ht5b (Htr5b) in the brainstem. Since 5-ht5b receptors couple to Gi proteins, we measured cAMP levels in brainstem tissue, and found that, unlike in WT and Mecp2-/y;Htr5b-/- mice, cAMP levels in Mecp2-/y mice were decreased. Using unrestrained whole-body plethysmography, we investigated, whether the persistence of 5-ht5b expression in older Mecp2-/y mice is contributing to the respiratory phenotype. The breathing of MeCP2-deficient male mice at postnatal day 40 was characterized by a slow breathing rate and the occurrence of prolonged respiratory pauses. In contrast, we found that both breathing rate and number of pauses in MeCP2-deficient mice, which also lacked the 5-ht5b receptor (Mecp2-/y;Htr5b-/-) was indistinguishable from wild type (WT) and Htr5b-/- mice. Taken together, our data points towards a role of 5-ht5b receptors within the breathing complex phenotype of MeCP2-deficient mice.
Keywords: MeCP2, cAMP, Respiration, 5-ht5b receptor, Rett Syndrome (RTT)
Received: 18 May 2017;
Accepted: 22 Jan 2018.
Edited by:Hansen Wang, University of Toronto, Canada
Reviewed by:Daniela Tropea, Trinity College, Dublin, Ireland
Erhard Wischmeyer, University of Würzburg, Germany
Nicoletta Landsberger, Università degli Studi di Milano, Italy
Copyright: © 2018 Vogelgesang, Niebert, Bischoff, Hülsmann and Manzke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Prof. Swen Hülsmann, Universitätsmedizin Göttingen, DFG-Research Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany, firstname.lastname@example.org
Dr. Till Manzke, Universitätsmedizin Göttingen, DFG-Research Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany, email@example.com