Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease

Abstract 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 m...

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Autores principales:	Valentina Cappello, Laura Marchetti, Paola Parlanti, Silvia Landi, Ilaria Tonazzini, Marco Cecchini, Vincenzo Piazza, Mauro Gemmi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2016
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c37d72751ae0467d9065e594228807fd
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spelling	oai:doaj.org-article:c37d72751ae0467d9065e594228807fd2021-12-02T12:32:21ZUltrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease10.1038/s41598-016-0001-82045-2322https://doaj.org/article/c37d72751ae0467d9065e594228807fd2016-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-016-0001-8https://doaj.org/toc/2045-2322Abstract 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.Valentina CappelloLaura MarchettiPaola ParlantiSilvia LandiIlaria TonazziniMarco CecchiniVincenzo PiazzaMauro GemmiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 6, Iss 1, Pp 1-15 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valentina Cappello Laura Marchetti Paola Parlanti Silvia Landi Ilaria Tonazzini Marco Cecchini Vincenzo Piazza Mauro Gemmi Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
description	Abstract 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.
format	article
author	Valentina Cappello Laura Marchetti Paola Parlanti Silvia Landi Ilaria Tonazzini Marco Cecchini Vincenzo Piazza Mauro Gemmi
author_facet	Valentina Cappello Laura Marchetti Paola Parlanti Silvia Landi Ilaria Tonazzini Marco Cecchini Vincenzo Piazza Mauro Gemmi
author_sort	Valentina Cappello
title	Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
title_short	Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
title_full	Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
title_fullStr	Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
title_full_unstemmed	Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
title_sort	ultrastructural characterization of the lower motor system in a mouse model of krabbe disease
publisher	Nature Portfolio
publishDate	2016
url	https://doaj.org/article/c37d72751ae0467d9065e594228807fd
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Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease

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