• Anton Filipchuk, Arnaud Pambo-Pambo, Fanny Gaudel, Sylvie Liabeuf, Cécile Brocard, Gueritaud Jean Patrick JP Institut de Neurosciences de la Timone, Equipe P3M, UMR 7289 CNRS-AMU, Aix Marseille Université, 27 Bd Jean Moulin, 13585 Marseille Cedex 20, Fr, and Jacques Durand.
• Institut de Neurosciences de la Timone, Equipe P3M, UMR 7289 CNRS-AMU, Aix Marseille Université, 27 Bd Jean Moulin, 13585 Marseille Cedex 20, France; Paris-Saclay Institute of Neuroscience (NeuroPSI), Department of Integrative and Computational Neuroscience (ICN), Centre National de la Recherche Scientifique (CNRS), 91198 Gif-sur-Yvette, France.
• Neuroscience. 2021 May 21; 463: 337-353.

AbstractIn amyotrophic lateral sclerosis (ALS), large motoneurons degenerate first, causing muscle weakness. Transgenic mouse models with a mutation in the gene encoding the enzyme superoxide dismutase 1 (SOD1) revealed that motoneurons innervating the fast-fatigable muscular fibres disconnect very early. The cause of this peripheric disconnection has not yet been established. Early pathological signs were described in motoneurons during the postnatal period of SOD1 transgenic mice. Here, we investigated whether the early changes of electrical and morphological properties previously reported in the SOD1G85R strain also occur in the SOD1G93A-low expressor line with particular attention to the different subsets of motoneurons defined by their discharge firing pattern (transient, sustained, or delayed-onset firing). Intracellular staining and recording were performed in lumbar motoneurons from entire brainstem-spinal cord preparations of SOD1G93A-low transgenic mice and their WT littermates during the second postnatal week. Our results show that SOD1G93A-low motoneurons exhibit a dendritic overbranching similar to that described previously in the SOD1G85R strain at the same age. Further we found an hypoexcitability in the delayed-onset firing SOD1G93A-low motoneurons (lower gain and higher voltage threshold). We conclude that dendritic overbranching and early hypoexcitability are common features of both low expressor SOD1 mutants (G85R and G93A-low). In the high-expressor SOD1G93A line, we found hyperexcitability in the sustained firing motoneurons at the same period, suggesting a delay in compensatory mechanisms. Overall, our results suggest that the hypoexcitability indicate an early dysfunction of the delayed-onset motoneurons and could account as early pathological signs of the disease.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

17 keywords...

hide…