101. Expression of ALS-linked SOD1 Mutation in Motoneurons or Myotubes Induces Differential Effects on Neuromuscular Function In vitro
- Author
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Claire Soulard, Vanessa Milla, Csilla Gergely, Melissa Bowerman, Salim Benlefki, Ana Sanchez-Vicente, Richard Younes, Frédérique Scamps, Olivier Lucas, Cécile Hilaire, Cédric Raoul, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuroscience Research Center [Beirut, Lebanon], Lebanese University [Beirut] (LU), Laboratoire Charles Coulomb (L2C), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Gene isoform ,RM ,animal structures ,[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] ,Muscle Fibers, Skeletal ,Amyotophic lateral sclerosis ,SOD1 ,Mice, Transgenic ,Biology ,Q1 ,medicine.disease_cause ,Neuromuscular junction ,Mice ,electrical activity ,03 medical and health sciences ,Superoxide Dismutase-1 ,0302 clinical medicine ,Myosin ,myotube contraction ,medicine ,Animals ,Myocyte ,mouse primary cell culture ,Amyotrophic lateral sclerosis ,Motor Neurons ,Mutation ,neuromuscular junction ,Superoxide Dismutase ,Myogenesis ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,fungi ,R735 ,Neurodegenerative Diseases ,RC346 ,musculoskeletal system ,medicine.disease ,R1 ,Cell biology ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,030217 neurology & neurosurgery - Abstract
International audience; 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 func- tional NMJs and fosters the expression of the ALS-sensitive fast fatigable type II-b myosin heavy chain (MHC) iso- form. Expression of SOD1G93A 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 SOD1G93A 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.
- Published
- 2020