{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:32:47Z","timestamp":1793932367084,"version":"4.8.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of \u03b2- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.<\/jats:p>","DOI":"10.1038\/s41598-016-0001-8","type":"journal-article","created":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T10:47:51Z","timestamp":1478861271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11649,"title":["Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Valentina","family":"Cappello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Parlanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Landi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7323-2174","authenticated-orcid":false,"given":"Ilaria","family":"Tonazzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cecchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Piazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Gemmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,5]]},"reference":[{"key":"1_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1093\/brain\/39.1-2.74","volume":"39","author":"K Krabbe","year":"1916","unstructured":"Krabbe, K. A new familial infantile form of diffuse brain-sclerosis. brain \n                           39, 74\u2013114 (1916).","journal-title":"brain"},{"key":"1_CR2","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s13311-011-0080-y","volume":"8","author":"ID Duncan","year":"2011","unstructured":"Duncan, I. D., Kondo, Y. & Zhang, S. C. The myelin mutants as models to study myelin repair in the leukodystrophies. Neurotherapeutics \n                           8, 607\u2013624, doi: 10.1007\/s13311-011-0080-y (2011).","journal-title":"Neurotherapeutics"},{"key":"1_CR3","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1523\/JNEUROSCI.3095-15.2016","volume":"36","author":"D Shin","year":"2016","unstructured":"Shin, D., Feltri, M. L. & Wrabetz, L. Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity. 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Psychosine accumulates in membrane microdomains in the brain of krabbe patients, disrupting the raft architecture. The Journal of neuroscience: the official journal of the Society for Neuroscience \n                           29, 6068\u20136077, doi: 10.1523\/JNEUROSCI.5597-08.2009 (2009).","journal-title":"The Journal of neuroscience : the official journal of the Society for Neuroscience"},{"key":"1_CR6","doi-asserted-by":"publisher","first-page":"e1529","DOI":"10.1038\/cddis.2014.483","volume":"5","author":"V Voccoli","year":"2014","unstructured":"Voccoli, V., Tonazzini, I., Signore, G., Caleo, M. & Cecchini, M. Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death. 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