{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:09:09Z","timestamp":1789985349731,"version":"4.0.1"},"reference-count":74,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T00:00:00Z","timestamp":1548806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["950\u2010230094"],"award-info":[{"award-number":["950\u2010230094"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CMA\u2010151727"],"award-info":[{"award-number":["CMA\u2010151727"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Myotonic dystrophy type 1 (DM1), the second most common muscular dystrophy and most prevalent adult form of muscular dystrophy, is characterized by muscle weakness, wasting and myotonia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A microsatellite repeat expansion mutation results in RNA toxicity and dysregulation of mRNA processing, which are the primary downstream causes of the disorder.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Recent studies with DM1 participants demonstrate that exercise is safe, enjoyable and elicits benefits in muscle strength and function; however, the molecular mechanisms of exercise adaptation in DM1 are undefined.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results demonstrate that 7\u00a0weeks of volitional running wheel exercise in a pre\u2010clinical DM1 mouse model resulted in significantly improved motor performance, muscle strength and endurance, as well as reduced myotonia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At the cellular level, chronic physical activity attenuated RNA toxicity, liberated Muscleblind\u2010like 1 protein from myonuclear foci and improved mRNA alternative splicing.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Myotonic dystrophy type 1 (DM1) is a trinucleotide repeat expansion neuromuscular disorder that is most prominently characterized by skeletal muscle weakness, wasting and myotonia. Chronic physical activity is safe and satisfying, and can elicit functional benefits such as improved strength and endurance in DM1 patients, but the underlying cellular basis of exercise adaptation is undefined. Our purpose was to examine the mechanisms of exercise biology in DM1. Healthy, sedentary wild\u2010type (SED\u2010WT) mice, as well as sedentary human skeletal actin\u2010long repeat animals, a murine model of DM1 myopathy (SED\u2010DM1), and DM1 mice with volitional access to a running wheel for 7\u00a0weeks (EX\u2010DM1), were utilized. Chronic exercise augmented strength and endurance <jats:italic>in vivo<\/jats:italic> and <jats:italic>in situ<\/jats:italic> in DM1 mice. These alterations coincided with normalized measures of myopathy, as well as increased mitochondrial content. Electromyography revealed a 70\u201385% decrease in the duration of myotonic discharges in muscles from EX\u2010DM1 compared to SED\u2010DM1 animals. The exercise\u2010induced enhancements in muscle function corresponded at the molecular level with mitigated spliceopathy, specifically the processing of bridging integrator 1 and muscle\u2010specific chloride channel (CLC\u20101) transcripts. CLC\u20101 protein content and sarcolemmal expression were lower in SED\u2010DM1 <jats:italic>versus<\/jats:italic> SED\u2010WT animals, but they were similar between SED\u2010WT and EX\u2010DM1 groups. Chronic exercise also attenuated RNA toxicity, as indicated by reduced (CUG)<jats:italic><jats:sub>n<\/jats:sub><\/jats:italic> foci\u2010positive myonuclei and sequestered Muscleblind\u2010like 1 (MBNL1). Our data indicate that chronic exercise\u2010induced physiological improvements in DM1 occur in concert with mitigated primary downstream disease mechanisms, including RNA toxicity, MBNL1 loss\u2010of\u2010function, and alternative mRNA splicing.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277123","type":"journal-article","created":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T11:35:20Z","timestamp":1547120120000},"page":"1361-1381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Chronic exercise mitigates disease mechanisms and improves muscle function in myotonic dystrophy type 1 mice"],"prefix":"10.1113","volume":"597","author":[{"given":"Alexander","family":"Manta","sequence":"first","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton ON Canada L8S 4K1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek 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