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 frst 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 fnd 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 fnd 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.

Ultrastructural characterization of the lower motor system in a mouse model of krabbe disease

Marchetti, Laura;Parlanti, Paola;Landi, Silvia;Tonazzini, Ilaria;Cecchini, Marco;
2016

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 frst 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 fnd 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 fnd 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.
2016
Animals; Disease Models, Animal; Leukodystrophy, Globoid Cell; Male; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Motor Neurons; Muscle, Skeletal; Muscular Atrophy; Nerve Degeneration; Neuromuscular Junction; Sciatic Nerve; Multidisciplinary
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/83368
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