Benlefki, S, Sanchez-Vicente, A, Milla, V, Lucas, O, Soulard, C, Younes, R, Gergely, C, Bowerman, M, Raoul, C, Scamps, F and Hilaire, C (2020) Expression of ALS-linked SOD1 mutation in motoneurons or myotubes induces differential effects on neuromuscular function in vitro. Neuroscience, 435. pp. 33-43. ISSN 1873-7544

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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.

Item Type: Article
Additional Information: The final accepted mauscript and all relevant information regarding this article can be found at;
Uncontrolled Keywords: amyotrophic lateral sclerosis, myotube contraction, electrical activity, mouse primary cell culture, neuromuscular junction
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RC Internal medicine > RC346 Neurology. Diseases of the nervous system, including speech disorders
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 27 Mar 2020 10:56
Last Modified: 29 Mar 2021 01:30

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