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Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b
Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). Although alteration in serotonin levels have been reported in RTT patients, the molecular mechanisms underlying these defects are not well unders...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340760/ https://www.ncbi.nlm.nih.gov/pubmed/28337123 http://dx.doi.org/10.3389/fnmol.2017.00061 |
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author | Vogelgesang, Steffen Niebert, Sabine Renner, Ute Möbius, Wiebke Hülsmann, Swen Manzke, Till Niebert, Marcus |
author_facet | Vogelgesang, Steffen Niebert, Sabine Renner, Ute Möbius, Wiebke Hülsmann, Swen Manzke, Till Niebert, Marcus |
author_sort | Vogelgesang, Steffen |
collection | PubMed |
description | Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). Although alteration in serotonin levels have been reported in RTT patients, the molecular mechanisms underlying these defects are not well understood. Therefore, we chose to investigate the serotonergic system in hippocampus and brainstem of male Mecp2(-/y) knock-out mice in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The serotonergic system in mouse is comprised of 16 genes, whose mRNA expression profile was analyzed by quantitative RT-PCR. Mecp2(-/y) mice are an established animal model for RTT displaying most of the cognitive and physical impairments of human patients and the selected areas receive significant modulation through serotonin. Using anatomically and functional characterized areas, we found region-specific differential expression between wild type and Mecp2(-/y) mice at post-natal day 40. In brainstem, we found five genes to be dysregulated, while in hippocampus, two genes were dysregulated. The one gene dysregulated in both brain regions was dopamine decarboxylase, but of special interest is the serotonin receptor 5b (5-ht(5b)), which showed 75-fold dysregulation in brainstem of Mecp2(-/y) mice. This dysregulation was not due to upregulation, but due to failure of down-regulation in Mecp2(-/y) mice during development. Detailed analysis of 5-ht(5b) revealed a receptor that localizes to endosomes and interacts with G(αi) proteins. |
format | Online Article Text |
id | pubmed-5340760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53407602017-03-23 Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b Vogelgesang, Steffen Niebert, Sabine Renner, Ute Möbius, Wiebke Hülsmann, Swen Manzke, Till Niebert, Marcus Front Mol Neurosci Neuroscience Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). Although alteration in serotonin levels have been reported in RTT patients, the molecular mechanisms underlying these defects are not well understood. Therefore, we chose to investigate the serotonergic system in hippocampus and brainstem of male Mecp2(-/y) knock-out mice in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The serotonergic system in mouse is comprised of 16 genes, whose mRNA expression profile was analyzed by quantitative RT-PCR. Mecp2(-/y) mice are an established animal model for RTT displaying most of the cognitive and physical impairments of human patients and the selected areas receive significant modulation through serotonin. Using anatomically and functional characterized areas, we found region-specific differential expression between wild type and Mecp2(-/y) mice at post-natal day 40. In brainstem, we found five genes to be dysregulated, while in hippocampus, two genes were dysregulated. The one gene dysregulated in both brain regions was dopamine decarboxylase, but of special interest is the serotonin receptor 5b (5-ht(5b)), which showed 75-fold dysregulation in brainstem of Mecp2(-/y) mice. This dysregulation was not due to upregulation, but due to failure of down-regulation in Mecp2(-/y) mice during development. Detailed analysis of 5-ht(5b) revealed a receptor that localizes to endosomes and interacts with G(αi) proteins. Frontiers Media S.A. 2017-03-08 /pmc/articles/PMC5340760/ /pubmed/28337123 http://dx.doi.org/10.3389/fnmol.2017.00061 Text en Copyright © 2017 Vogelgesang, Niebert, Renner, Möbius, Hülsmann, Manzke and Niebert. http://creativecommons.org/licenses/by/4.0/ 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) or licensor 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. |
spellingShingle | Neuroscience Vogelgesang, Steffen Niebert, Sabine Renner, Ute Möbius, Wiebke Hülsmann, Swen Manzke, Till Niebert, Marcus Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b |
title | Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b |
title_full | Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b |
title_fullStr | Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b |
title_full_unstemmed | Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b |
title_short | Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b |
title_sort | analysis of the serotonergic system in a mouse model of rett syndrome reveals unusual upregulation of serotonin receptor 5b |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340760/ https://www.ncbi.nlm.nih.gov/pubmed/28337123 http://dx.doi.org/10.3389/fnmol.2017.00061 |
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