Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease

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dc.contributor.authorBrisendine, Matthew H.en
dc.contributor.authorNichenko, Anna S.en
dc.contributor.authorBandara, Aloka B.en
dc.contributor.authorWilloughby, Orion S.en
dc.contributor.authorAmiri, Niloufaren
dc.contributor.authorWeingrad, Zachen
dc.contributor.authorSpecht, Kalyn S.en
dc.contributor.authorBond, Jacob M.en
dc.contributor.authorAddington, Adeleen
dc.contributor.authorJones III, Ronald G.en
dc.contributor.authorMurach, Kevin A.en
dc.contributor.authorPoelzing, Stevenen
dc.contributor.authorCraige, Siobhan M.en
dc.contributor.authorGrange, Robert W.en
dc.contributor.authorDrake, Joshua C.en
dc.date.accessioned2024-02-19T18:23:14Zen
dc.date.available2024-02-19T18:23:14Zen
dc.date.issued2023-12-04en
dc.description.abstractAlzheimer's disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur years earlier in those that develop AD; however, it is unknown what causes these peripheral phenotypes in a disease of the brain. Exercise promotes muscle, mitochondria, and cognitive health and is proposed to be a potential therapeutic for AD, but no study has investigated how skeletal muscle adapts to exercise training in an AD-like context. Utilizing 5xFAD mice, an AD model that develops ad-like pathology and cognitive impairments around 6 mo of age, we examined in vivo neuromuscular function and exercise adapations (mitochondrial respiration and RNA sequencing) before the manifestation of overt cognitive impairment. We found 5xFAD mice develop neuromuscular dysfunction beginning as early as 4 mo of age, characterized by impaired nerve-stimulated muscle torque production and compound nerve action potential of the sciatic nerve. Furthermore, skeletal muscle in 5xFAD mice had altered, sex-dependent, adaptive responses (mitochondrial respiration and gene expression) to exercise training in the absence of overt cognitive impairment. Changes in peripheral systems, specifically neural communication to skeletal muscle, may be harbingers for AD and have implications for lifestyle interventions, like exercise, in AD.en
dc.description.versionPublished versionen
dc.format.extent11 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN zqad066 (Article number)en
dc.identifier.doihttps://doi.org/10.1093/function/zqad066en
dc.identifier.eissn2633-8823en
dc.identifier.issn2633-8823en
dc.identifier.issue1en
dc.identifier.orcidPoelzing, Steven [0000-0002-6979-1264]en
dc.identifier.orcidDrake, Joshua [0000-0001-6658-4975]en
dc.identifier.orcidGrange, Robert [0000-0002-8288-2793]en
dc.identifier.otherzqad066 (PII)en
dc.identifier.pmid38111538en
dc.identifier.urihttps://hdl.handle.net/10919/118038en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/38111538en
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectexerciseen
dc.subjectneuromuscularen
dc.subjectmitochondriaen
dc.subjectsciatic nerveen
dc.subjectAlzheimer's diseaseen
dc.subject.meshBrainen
dc.subject.meshMitochondriaen
dc.subject.meshAnimalsen
dc.subject.meshMice, Transgenicen
dc.subject.meshMiceen
dc.subject.meshAlzheimer Diseaseen
dc.subject.meshCognitive Dysfunctionen
dc.titleNeuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Diseaseen
dc.title.serialFunctionen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2023-11-26en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exerciseen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Secondary Appointment- Internal Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Internal Med-Subgroupen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Biomedical Research Institute at VTCen

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