Investigating the role of interleukin-6 in neuronal dysfunction in the mdx mouse model of Duchenne muscular dystrophy

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dc.availability.bitstreamembargoed
dc.check.date2026-05-31
dc.contributor.advisorO'Malley, Dervlaen
dc.contributor.advisorRae, Marken
dc.contributor.authorStephenson, Kimberley Alix
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2023-01-24T10:23:46Z
dc.date.available2023-01-24T10:23:46Z
dc.date.issued2022-01-07
dc.date.submitted2022-01-07
dc.description.abstractDuchenne Muscular Dystrophy (DMD) is a fatal musculoskeletal disorder that results in a loss of dystrophin in muscle fibres, leading to progressive immobility, chronic inflammation and premature death. Inflammation is characterised by increased circulating levels of pro-inflammatory cytokines such as IL-6. However, it is apparent that dystrophin not only functions in skeletal muscle, but in the CNS as well, with an increased incidence of cognitive impairment and deficits in verbal, short-term and working memory in individuals with DMD. The hippocampus is critical for learning and the formation and consolidation of memories and can be modified by neuroimmune cytokines, such as IL-6. The aim of this programme of research was to investigate the possible contribution of the neuroimmune molecule, IL-6 in cognitive impairment associated with loss of the structural protein, dystrophin. Initially, we used the dystrophic mdx mouse to investigate what impact loss of dystrophin had on normal hippocampal function. Significantly, LTP, the molecular correlate of learning and memory was shown to be decreased in mdx mice, which has been linked to memory dysfunction. Moreover, changes in the density and structure of mdx hippocampal neurons and glia was observed over time. Subsequently, we examined the possible effects of IL-6 on hippocampal function in mdx mice. IL-6 and IL-6R expression were altered in specific regions in the hippocampus, which underpins function relating to learning and memory. Indeed, in vivo blockade of IL-6-mediated signalling in the CNS of mdx mice restored LTP, although at this age, it did not impact on learning behaviours. These studies have elucidated previously unknown cellular and molecular changes in the hippocampus of dystrophin-deficient mice. Moreover, we have linked the neuromodulatory cytokine, IL-6, with the observed pathophysiology.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationStephenson, K. A. 2022. Investigating the role of interleukin-6 in neuronal dysfunction in the mdx mouse model of Duchenne muscular dystrophy. PhD Thesis, University College Cork.en
dc.identifier.endpage218en
dc.identifier.urihttps://hdl.handle.net/10468/14118
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectHealth Research Board (Investigator Led Project ILP-POR-2017-040)en
dc.rights© 2022, Kimberley Alix Stephenson.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectDMDen
dc.subjectIL-6en
dc.subjectLTPen
dc.subjectCognitive impairmenten
dc.titleInvestigating the role of interleukin-6 in neuronal dysfunction in the mdx mouse model of Duchenne muscular dystrophyen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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