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Article Dans Une Revue Neuromuscular Disorders Année : 2014

Advances in the understanding of skeletal muscle weakness in murine models of diseases affecting nerve-evoked muscle activity, motor neurons, synapses and myofibers

Arnaud Ferry
Pierre Joanne
Wahiba Hadj-Said
  • Fonction : Auteur
Alban Vignaud
  • Fonction : Auteur
Alain Lilienbaum
Christophe Hourde
  • Fonction : Auteur
Fadia Medja
  • Fonction : Auteur
Philippe Noirez
Frederic Charbonnier
  • Fonction : Auteur
Arnaud Chatonnet
Frederic Chevessier
  • Fonction : Auteur
Sophie Nicole
Onnik Agbulut
Gillian Butler-Browne

Résumé

Disease processes and trauma affecting nerve-evoked muscle activity, motor neurons, synapses and myofibers cause different levels of muscle weakness, i.e., reduced maximal force production in response to voluntary activation or nerve stimulation. However, the mechanisms of muscle weakness are not well known. Using murine models of amyotrophic lateral sclerosis (SOD1(G93) transgenic mice), congenital myasthenic syndrome (AChE knockout mice and Musk(V789m/-) mutant mice), Schwartz Jampel syndrome (Hspg2(C1532YNEO/C1532YNEO) mutant mice) and traumatic nerve injury (Neurotomized wild-type mice), we show that the reduced maximal activation capacity (the ability of the nerve to maximally activate the muscle) explains 52%, 58% and 100% of severe weakness in respectively SOD1(G93A), Neurotomized and Musk mice, whereas muscle atrophy only explains 37%, 27% and 0%. We also demonstrate that the impaired maximal activation capacity observed in SOD 1, Neurotomized, and Musk mice is not highly related to Hdac4 gene upregulation. Moreover, in SOD1 and Neurotomized mice our results suggest LC3, Fn14, Bcl3 and Gadd45a as candidate genes involved in the maintenance of the severe atrophic state. In conclusion, our study indicates that muscle weakness can result from the triggering of different signaling pathways. This knowledge may be helpful in designing therapeutic strategies and finding new drug targets for amyotrophic lateral sclerosis, congenital myasthenic syndrome, Schwartz Jampel syndrome and nerve injury.
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Dates et versions

hal-01545452 , version 1 (22-06-2017)

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Citer

Arnaud Ferry, Pierre Joanne, Wahiba Hadj-Said, Alban Vignaud, Alain Lilienbaum, et al.. Advances in the understanding of skeletal muscle weakness in murine models of diseases affecting nerve-evoked muscle activity, motor neurons, synapses and myofibers. Neuromuscular Disorders, 2014, 24 (11), pp.960-972. ⟨10.1016/j.nmd.2014.06.001⟩. ⟨hal-01545452⟩
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