Respiratory control in the mdx mouse model of Duchenne muscular dystrophy

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dc.contributor.advisor O'Halloran, Ken D. en Burns, David P. 2018-09-20T08:57:06Z 2018-09-20T08:57:06Z 2018 2018
dc.identifier.citation Burns, D. P. 2018. Respiratory control in the mdx mouse model of Duchenne muscular dystrophy. PhD Thesis, University College Cork. en
dc.identifier.endpage 303 en
dc.description.abstract Duchenne muscular dystrophy (DMD) is a genetic disease that occurs in males due to the absence of the dystrophin (427 kDa) protein. Comprehensive studies on the control of breathing in DMD and animal models of the dystrophinopathies are lacking. We examined the integrated respiratory control system in a pre-clinical model of DMD – the mdx mouse. Young (8-week-old) wild-type and mdx mice were studied. During normoxia, mdx mice hypoventilated, due to decreased tidal volume with no evidence of perturbed respiratory rhythm. Carotid sinus nerve responses to hyperoxia were blunted in mdx, suggesting hypoactivity (sensory deficit). Mdx mice retained a remarkable capacity to increase ventilation during hypercapnic hypoxic breathing despite profound diaphragm muscle weakness and major structural remodelling. Peak inspiratory oesophageal pressure generation was preserved in mdx compared to wild-type mice, probably due to recruitment of accessory muscles of breathing. Monoamine concentrations were elevated in the C3-C5 spinal cord of mdx mice, and the density of activated immune cells and pro-inflammatory gene expression was unchanged, indicating no evidence of neuroinflammation. xIL-6R and Ucn2 co-treatment in mdx mice completely restored ventilation and significantly improved diaphragm and sternohyoid muscle strength. Combinational therapy restored myosin heavy chain complement in respiratory muscles. Considerable deficits arising from dystrophin lack are partly compensated, limiting ventilatory deficits in young mdx mice. Strategies aimed at preserving muscle fibre complement and quality in mdx respiratory muscles can alleviate breathing and muscle functional deficits. These data may have relevance to the development of treatments for the human dystrophinopathies. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2018, David P. Burns. en
dc.rights.uri en
dc.subject Duchenne muscular dystrophy en
dc.subject mdx en
dc.subject Breathing en
dc.subject Diaphragm en
dc.subject EMG en
dc.subject Upper airway en
dc.subject Interleukin-6 en
dc.subject Urocortin en
dc.title Respiratory control in the mdx mouse model of Duchenne muscular dystrophy en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text available en Not applicable en
dc.description.version Accepted Version
dc.description.status Not peer reviewed en Physiology en
dc.check.type No Embargo Required
dc.check.reason Not applicable en
dc.check.opt-out No en
dc.thesis.opt-out false
dc.check.embargoformat Embargo not applicable (If you have not submitted an e-thesis or do not want to request an embargo) en
dc.internal.conferring Autumn 2018 en

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© 2018, David P. Burns. Except where otherwise noted, this item's license is described as © 2018, David P. Burns.
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