Respiratory control in the mdx mouse model of Duchenne muscular dystrophy

Simple item page
dc.check.embargoformatEmbargo not applicable (If you have not submitted an e-thesis or do not want to request an embargo)en
dc.check.infoNot applicableen
dc.check.opt-outNoen
dc.check.reasonNot applicableen
dc.check.typeNo Embargo Required
dc.contributor.advisorO'Halloran, Ken D.en
dc.contributor.authorBurns, David P.
dc.date.accessioned2018-09-20T08:57:06Z
dc.date.available2018-09-20T08:57:06Z
dc.date.issued2018
dc.date.submitted2018
dc.description.abstractDuchenne 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.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBurns, D. P. 2018. Respiratory control in the mdx mouse model of Duchenne muscular dystrophy. PhD Thesis, University College Cork.en
dc.identifier.endpage303en
dc.identifier.urihttps://hdl.handle.net/10468/6821
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2018, David P. Burns.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectDuchenne muscular dystrophyen
dc.subjectmdxen
dc.subjectBreathingen
dc.subjectDiaphragmen
dc.subjectEMGen
dc.subjectUpper airwayen
dc.subjectInterleukin-6en
dc.subjectUrocortinen
dc.thesis.opt-outfalse
dc.titleRespiratory control in the mdx mouse model of Duchenne muscular dystrophyen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhDen
ucc.workflow.supervisork.ohalloran@ucc.ie
Files
Original bundle
Now showing 1 - 3 of 3
Thumbnail Image
Name:
BurnsDP_PhD2018_ Abstract.pdf
Size:
218.45 KB
Format:
Adobe Portable Document Format
Description:
Abstract
Thumbnail Image
Name:
BurnsDP_PhD2018_ethesis.pdf
Size:
6.18 MB
Format:
Adobe Portable Document Format
Description:
Full Text E-thesis
Download
Thumbnail Image
Name:
BurnsDP_PhD2018_word_ethesis.docx
Size:
17.56 MB
Format:
Microsoft Word XML
Description:
Full Text E-thesis (Word)
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
5.62 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Doctoral Theses
College of Medicine and Health - Doctoral Theses
Physiology - Doctoral Theses