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Expression of ALS-linked SOD1 mutation in motoneurons or myotubes induces differential effects on neuromuscular function in vitro

Benlefki, Salim; Sanchez-Vicente, Ana; Milla, Vanessa; Lucas, Olivier; Soulard, Claire; Younes, Richard; Gergely, Csilla; Bowerman, Mélissa; Raoul, Cédric; Scamps, Frédérique; Hilaire, Cécile

Expression of ALS-linked SOD1 mutation in motoneurons or myotubes induces differential effects on neuromuscular function in vitro Thumbnail


Authors

Salim Benlefki

Ana Sanchez-Vicente

Vanessa Milla

Olivier Lucas

Claire Soulard

Richard Younes

Csilla Gergely

Cédric Raoul

Frédérique Scamps

Cécile Hilaire



Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively affects upper and lower motoneurons. Dismantlement of the neuromuscular junction (NMJ) is an early pathological hallmark of the disease whose cellular origin remains still debated. We developed an in vitro NMJ model to investigate the differential contribution of motoneurons and muscle cells expressing ALS-causing mutation in the superoxide dismutase 1 (SOD1) to neuromuscular dysfunction. The primary co-culture system allows the formation of functional NMJs and fosters the expression of the ALS-sensitive fast fatigable type II-b myosin heavy chain (MHC) isoform. Expression of SOD1(G93A) in myotubes does not prevent the formation of a functional NMJ but leads to decreased contraction frequency and lowers the slow type I MHC isoform transcript levels. Expression of SOD1(G93A) in both motoneurons and myotubes or in motoneurons alone however alters the formation of a functional NMJ. Our results strongly suggest that motoneurons are a major factor involved in the process of NMJ dismantlement in an experimental model of ALS.

Journal Article Type Article
Acceptance Date Mar 26, 2020
Online Publication Date Mar 29, 2020
Publication Date May 21, 2020
Publicly Available Date May 26, 2023
Journal Neuroscience
Print ISSN 0306-4522
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 435
Pages 33-43
DOI https://doi.org/10.1016/j.neuroscience.2020.03.044
Keywords amyotrophic lateral sclerosis, myotube contraction, electrical activity, mouse primary cell culture,neuromuscular junction
Publisher URL https://doi.org/10.1016/j.neuroscience.2020.03.044

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