Journal
NEUROSCIENCE
Volume 435, Issue -, Pages 33-43Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2020.03.044
Keywords
amyotophic lateral sclerosis; myotube contraction; electrical activity; mouse primary cell culture; neuromuscular junction
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Funding
- Institut National de la Santeet de la Recherche Medicale (Inserm)
- association pour la recherche sur la SLA (ARSLA) [R14071FF]
- ANR Mimetic [15CE18-0017]
- association francaise contre les myopathies (AFM) [19496]
- LabEx NUMEV [ANR-10-LABX-20]
- Lebanese University
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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. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
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