Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy.

Détails

Ressource 1Télécharger: BIB_01818AF4B545.P001.pdf (1060.18 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_01818AF4B545
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy.
Périodique
Disease Models and Mechanisms
Auteur(s)
Panaite P.A., Kuntzer T., Gourdon G., Lobrinus J.A., Barakat-Walter I.
ISSN
1754-8411 (Electronic)
ISSN-L
1754-8403
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
6
Numéro
3
Pages
622-631
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding mechanisms of respiratory deficiency should guide pharmaceutical and clinical research towards better therapy for the respiratory deficits associated with DM1.
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/06/2013 17:56
Dernière modification de la notice
20/08/2019 13:23
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