{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:08:05Z","timestamp":1790665685903,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Blue Sky Research (Call for University Research Found)","award":["BSR-15214"],"award-info":[{"award-number":["BSR-15214"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons leading to muscle weakness and respiratory failure. Mitochondrial dysfunctions are found in the skeletal muscle of patients with SMA. For obvious ethical reasons, the diaphragm muscle is poorly studied, notwithstanding the very important role that respiratory involvement plays in SMA mortality. The main goal of this study was to investigate diaphragm functionality and the underlying molecular adaptations in SMN\u03947 mice, a mouse model that exhibits symptoms similar to that of patients with intermediate type II SMA. Functional, biochemical, and molecular analyses on isolated diaphragm were performed. The obtained results suggest the presence of an intrinsic energetic imbalance associated with mitochondrial dysfunction and a significant accumulation of reactive oxygen species (ROS). In turn, ROS accumulation can affect muscle fatigue, cause diaphragm wasting, and, in the long run, respiratory failure in SMN\u03947 mice. Exposure to the antioxidant molecule ergothioneine leads to the functional recovery of the diaphragm, confirming the presence of mitochondrial impairment and redox imbalance. These findings suggest the possibility of carrying out a dietary supplementation in SMN\u03947 mice to preserve their diaphragm function and increase their lifespan.<\/jats:p>","DOI":"10.3390\/ijms241914953","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:49:29Z","timestamp":1696578569000},"page":"14953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Diaphragm Fatigue in SMN\u03947 Mice and Its Molecular Determinants: An Underestimated Issue"],"prefix":"10.3390","volume":"24","author":[{"given":"Francesca","family":"Cadile","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, via Forlanini 6, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-5165","authenticated-orcid":false,"given":"Deborah","family":"Recchia","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2578-7393","authenticated-orcid":false,"given":"Massimiliano","family":"Ansaldo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, via Forlanini 6, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-7519","authenticated-orcid":false,"given":"Giorgia","family":"Rastelli","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-5069","authenticated-orcid":false,"given":"Simona","family":"Boncompagni","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-0573","authenticated-orcid":false,"given":"Lorenza","family":"Brocca","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, via Forlanini 6, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-1266","authenticated-orcid":false,"given":"Maria Antonietta","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, via Forlanini 6, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Canepari","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, via Forlanini 6, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S245","DOI":"10.1542\/peds.2008-2952K","article-title":"Special considerations in the respiratory management of spinal muscular atrophy","volume":"123","author":"Schroth","year":"2009","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1097\/MOP.0b013e32833f3046","article-title":"Spinal muscular atrophy: A time for screening","volume":"22","author":"Prior","year":"2010","journal-title":"Curr. 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