{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:23:34Z","timestamp":1790508214221,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000192","name":"Ontario Ministry of Economic Development and Innovation","doi-asserted-by":"publisher","award":["ER17\u201013\u2010087"],"award-info":[{"award-number":["ER17\u201013\u2010087"]}],"id":[{"id":"10.13039\/501100000192","id-type":"DOI","asserted-by":"publisher"}]},{"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":[[2019,9]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Spinal muscular atrophy (SMA) is a health\u2010 and life\u2010limiting neuromuscular disorder caused by a deficiency in survival motor neuron (SMN) protein.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>While historically considered a motor neuron disease, current understanding of SMA emphasizes its systemic nature, which requires addressing affected peripheral tissues such as skeletal muscle in particular.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Chronic physical activity is beneficial for SMA patients, but the cellular and molecular mechanisms of exercise biology are largely undefined in SMA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>After a single bout of exercise, canonical responses such as skeletal muscle AMP\u2010activated protein kinase (AMPK), p38 mitogen\u2010activated protein kinase (p38) and peroxisome proliferator\u2010activated receptor \u03b3 coactivator 1\u03b1 (PGC\u20101\u03b1) activation were preserved in SMA\u2010like <jats:italic>Smn<jats:sup>2B\/\u2212<\/jats:sup><\/jats:italic> animals. Furthermore, molecules involved in SMN transcription were also altered following physical activity. Collectively, these changes were coincident with an increase in full\u2010length SMN transcription and corrective SMN pre\u2010mRNA splicing.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study advances understanding of the exercise biology of SMA and highlights the AMPK\u2013p38\u2013PGC\u20101\u03b1 axis as a potential regulator of SMN expression in muscle.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Chronic physical activity is safe and effective in spinal muscular atrophy (SMA) patients, but the underlying cellular events that drive physiological adaptations are undefined. We examined the effects of a single bout of exercise on molecular mechanisms associated with adaptive remodelling in the skeletal muscle of <jats:italic>Smn<jats:sup>2B\/\u2212<\/jats:sup><\/jats:italic> SMA\u2010like mice. Skeletal muscles were collected from healthy <jats:italic>Smn<jats:sup>2B\/+<\/jats:sup><\/jats:italic> mice and <jats:italic>Smn<jats:sup>2B\/\u2212<\/jats:sup><\/jats:italic> littermates at pre\u2010 (postnatal day (P) 9), early\u2010 (P13) and late\u2010 (P21) symptomatic stages to characterize SMA disease progression. Muscles were also collected from <jats:italic>Smn<jats:sup>2B\/\u2212<\/jats:sup><\/jats:italic> animals exercised to fatigue on a motorized treadmill. Intracellular signalling and gene expression were examined using western blotting, confocal immunofluorescence microscopy, real\u2010time quantitative PCR and endpoint PCR assays. Basal skeletal muscle AMP\u2010activated protein kinase (AMPK) and p38 mitogen\u2010activated protein kinase (p38) expression and activity were not affected by SMA\u2010like conditions. Canonical exercise responses such as AMPK, p38 and peroxisome proliferator\u2010activated receptor \u03b3 coactivator\u20101\u03b1 (PGC\u20101\u03b1) activation were observed following a bout of exercise in <jats:italic>Smn<jats:sup>2B\/\u2212<\/jats:sup><\/jats:italic> animals. Furthermore, molecules involved in survival motor neuron (SMN) transcription, including protein kinase B (AKT) and extracellular signal\u2010regulated kinases (ERK)\/ETS\u2010like gene 1 (ELK1), were altered following physical activity. Acute exercise was also able to mitigate aberrant proteolytic signalling in the skeletal muscle of <jats:italic>Smn<jats:sup>2B\/\u2212<\/jats:sup><\/jats:italic> mice. Collectively, these changes were coincident with an exercise\u2010evoked increase in full\u2010length SMN mRNA expression. This study advances our understanding of the exercise biology of SMA and highlights the AMPK\u2013p38\u2013PGC\u20101\u03b1 axis as a potential regulator of SMN expression alongside AKT and ERK\/ELK1 signalling.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278454","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T09:33:29Z","timestamp":1564479209000},"page":"4757-4778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mechanisms of exercise\u2010induced survival motor neuron expression in the skeletal muscle of spinal muscular atrophy\u2010like mice"],"prefix":"10.1113","volume":"597","author":[{"given":"Sean Y.","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario 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