Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
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Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- 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.
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- Authors
- Cappello, V., Marchetti, L., Parlanti, P., Landi, S., Tonazzini, I., Cecchini, M., Piazza, V., & Gemmi, M.
- Affiliations
- Italian Institute of Technology (IT)
- Scuola Normale Superiore (IT)
- Istituto Nanoscienze (IT)
- Corresponding author
- Cappello, Valentina
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-12-05
- Volume
- 6
- Issue
- 1
- Pages
- 1-1
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5431369
- OpenAlex
- W2549976854
- Cited by
- 13,097
- References
- 44
- Citations by year
- 2026: 111 · 2025: 728 · 2024: 1065 · 2023: 1985 · 2022: 2515 · 2021: 2867 · 2020: 1636 · 2019: 968 · 2018: 712 · 2017: 424 · 2016: 80 · 2012: 1
- FWCI
- 585.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Scuola Normale Superiore di Pisa (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- Krabbe disease, neuromuscular junction, dying-back degeneration, galactosylceramidase deficiency, galactosylsphingosine, motor defects, postnatal development
- MeSH terms
- Animals, Disease Models, Animal, Leukodystrophy, Globoid Cell, Male, Mice, Inbred C57BL, Motor Neurons, Muscular Atrophy, Nerve Degeneration, Neuromuscular Junction, Sciatic Nerve, Muscle, Skeletal, Microscopy, Electron, Transmission
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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