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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

Authors :
Elisabetta Golini
Mara Rigamonti
Marcello Raspa
Ferdinando Scavizzi
Germana Falcone
Genevieve Gourdon
Silvia Mandillo
Source :
Frontiers in Behavioral Neuroscience, Vol 17 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

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.

Details

Language :
English
ISSN :
16625153
Volume :
17
Database :
Directory of Open Access Journals
Journal :
Frontiers in Behavioral Neuroscience
Publication Type :
Academic Journal
Accession number :
edsdoj.b5aa180ebb8459ebfc0f7d283fb6e4e
Document Type :
article
Full Text :
https://doi.org/10.3389/fnbeh.2023.1130055