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Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring

Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3′-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-re...

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Autores principales: Golini, Elisabetta, Rigamonti, Mara, Raspa, Marcello, Scavizzi, Ferdinando, Falcone, Germana, Gourdon, Genevieve, Mandillo, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017452/
https://www.ncbi.nlm.nih.gov/pubmed/36935893
http://dx.doi.org/10.3389/fnbeh.2023.1130055
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author Golini, Elisabetta
Rigamonti, Mara
Raspa, Marcello
Scavizzi, Ferdinando
Falcone, Germana
Gourdon, Genevieve
Mandillo, Silvia
author_facet Golini, Elisabetta
Rigamonti, Mara
Raspa, Marcello
Scavizzi, Ferdinando
Falcone, Germana
Gourdon, Genevieve
Mandillo, Silvia
author_sort Golini, Elisabetta
collection PubMed
description Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3′-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-respiratory problems, hypersomnia, cognitive dysfunction and behavioral abnormalities. Sleep-related disturbances are among the most reported symptoms that negatively affect the quality of life of patients and that are present in early and adult-onset forms of the disease. DMSXL mice carry a mutated human DMPK transgene containing >1,000 CTGrepeats, modeling an early onset, severe form of DM1. They exhibit a pathologic neuromuscular phenotype and also synaptic dysfunction resulting in neurological and behavioral deficits similar to those observed in patients. Additionally, they are underweight with a very high mortality within the first month after birth presenting several welfare issues. To specifically explore sleep/rest-related behaviors of this frail DM1 mouse model we used an automated home cage-based system that allows 24/7 monitoring of their activity non-invasively. We tested male and female DMSXL mice and their wild-type (WT) littermates in Digital Ventilated Cages (DVCR) assessing activity and rest parameters on day and night for 5 weeks. We demonstrated that DMSXL mice show reduced activity and regularity disruption index (RDI), higher percentage of zero activity per each hour and longer periods of rest during the active phase compared to WT. This novel rest-related phenotype in DMSXL mice, assessed unobtrusively, could be valuable to further explore mechanisms and potential therapeutic interventions to alleviate the very common symptom of excessive daytime sleepiness in DM1 patients.
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spelling pubmed-100174522023-03-17 Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring Golini, Elisabetta Rigamonti, Mara Raspa, Marcello Scavizzi, Ferdinando Falcone, Germana Gourdon, Genevieve Mandillo, Silvia Front Behav Neurosci Neuroscience Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3′-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-respiratory problems, hypersomnia, cognitive dysfunction and behavioral abnormalities. Sleep-related disturbances are among the most reported symptoms that negatively affect the quality of life of patients and that are present in early and adult-onset forms of the disease. DMSXL mice carry a mutated human DMPK transgene containing >1,000 CTGrepeats, modeling an early onset, severe form of DM1. They exhibit a pathologic neuromuscular phenotype and also synaptic dysfunction resulting in neurological and behavioral deficits similar to those observed in patients. Additionally, they are underweight with a very high mortality within the first month after birth presenting several welfare issues. To specifically explore sleep/rest-related behaviors of this frail DM1 mouse model we used an automated home cage-based system that allows 24/7 monitoring of their activity non-invasively. We tested male and female DMSXL mice and their wild-type (WT) littermates in Digital Ventilated Cages (DVCR) assessing activity and rest parameters on day and night for 5 weeks. We demonstrated that DMSXL mice show reduced activity and regularity disruption index (RDI), higher percentage of zero activity per each hour and longer periods of rest during the active phase compared to WT. This novel rest-related phenotype in DMSXL mice, assessed unobtrusively, could be valuable to further explore mechanisms and potential therapeutic interventions to alleviate the very common symptom of excessive daytime sleepiness in DM1 patients. Frontiers Media S.A. 2023-03-02 /pmc/articles/PMC10017452/ /pubmed/36935893 http://dx.doi.org/10.3389/fnbeh.2023.1130055 Text en Copyright © 2023 Golini, Rigamonti, Raspa, Scavizzi, Falcone, Gourdon and Mandillo. https://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) and the copyright owner(s) 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
Golini, Elisabetta
Rigamonti, Mara
Raspa, Marcello
Scavizzi, Ferdinando
Falcone, Germana
Gourdon, Genevieve
Mandillo, Silvia
Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
title Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
title_full Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
title_fullStr Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
title_full_unstemmed Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
title_short Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
title_sort excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017452/
https://www.ncbi.nlm.nih.gov/pubmed/36935893
http://dx.doi.org/10.3389/fnbeh.2023.1130055
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