{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:44:11Z","timestamp":1787499851779,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2015MJBEM2_006"],"award-info":[{"award-number":["2015MJBEM2_006"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biometec, University of Catania, Italy","award":["International PhD program in Neuroscience"],"award-info":[{"award-number":["International PhD program in Neuroscience"]}]},{"name":"Biometec, University of Catania, Italy","award":["no. 4474\/2017"],"award-info":[{"award-number":["no. 4474\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Although motoneuronal loss is the critical hallmark of ALS given their specific vulnerability, other cell populations, including muscle and glial cells, are involved in disease onset and progression, but unraveling their specific role and crosstalk requires further investigation. In particular, little is known about the plastic changes of the degenerating motor system. These spontaneous compensatory processes are unable to halt the disease progression, but their elucidation and possible use as a therapeutic target represents an important aim of ALS research. Genetic animal models of disease represent useful tools to validate proven hypotheses or to test potential therapies, and the conception of novel hypotheses about ALS causes or the study of pathogenic mechanisms may be advantaged by the use of relatively simple in vivo models recapitulating specific aspects of the disease, thus avoiding the inclusion of too many confounding factors in an experimental setting. Here, we used a neurotoxic model of spinal motoneuron depletion induced by injection of cholera toxin-B saporin in the gastrocnemius muscle to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord. The results showed that, following the lesion, the skeletal muscle became atrophic and displayed electromyographic activity similar to that observed in ALS patients. Moreover, the changes in muscle fiber morphology were different from that observed in ALS models, thus suggesting that some muscular effects of disease may be primary effects instead of being simply caused by denervation. Notably, we found plastic changes in the surviving motoneurons that can produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be at least partially driven by glutamatergic signaling, and astrocytes contacting the surviving motoneurons may support this process.<\/jats:p>","DOI":"10.3390\/ijms20061500","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T05:03:12Z","timestamp":1553662992000},"page":"1500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8067-697X","authenticated-orcid":false,"given":"Rosario","family":"Gulino","sequence":"first","affiliation":[{"name":"Laboratory of Neurophysiology, Department of Biomedical and Biotechnological Science, Section of Physiology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-3962","authenticated-orcid":false,"given":"Nunzio","family":"Vicario","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Physiology, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.S.","family":"Giunta","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Physiology, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Spoto","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Physiology, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1937-5403","authenticated-orcid":false,"given":"Giovanna","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Physiology, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, \u201cAOU Policlinico Vittorio Emanuele\u201d and Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-1745","authenticated-orcid":false,"given":"Massimo","family":"Gulisano","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic and Systems Biology, Department of Drug Sciences, University of Catania, Catania 95125, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampiero","family":"Leanza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenesis and Repair, Department of Drug Sciences, University of Catania, Catania 95125, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1614-4696","authenticated-orcid":false,"given":"Rosalba","family":"Parenti","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Physiology, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.14336\/AD.2013.0400295","article-title":"Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials","volume":"4","author":"Gordon","year":"2013","journal-title":"Aging Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3109\/17482960802566824","article-title":"Prognostic factors in ALS: A critical review","volume":"10","author":"Chio","year":"2009","journal-title":"Amyotroph. 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