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Rôle du canal chlorure activé par le calcium TMEM16F dans la motricité et implication dans la sclérose latérale amyotrophique

Abstract : Spinal motoneurons have a prominent place in motor system. Motoneurons integrate all inputs from the central and peripheral nervous systems to construct a motor output adapted to the organism's demands and environmental constraints. In particular, recruitment threshold and firing frequency are key motoneuronal parameters in developing an appropriate signal regarding task-dependent demands. During muscle activity, motor units are orderly recruited beginning with slow-type (S) motor units for posture maintenance, followed by fast-type motor units for moderate intensity tasks (FR) and high intensity tasks (FF). Our study highlights a new factor involved in the regulation of motoneuron excitability. This refers to a calcium-activated chloride channel called TMEM16F, specifically expressed in α motoneurons at cholinergic C-bouton synapse. Likewise C-boutons, TMEM16F is required for the procution of high intensity effort. Indeed, in accordance with electrophysiological recordings showing an increase in recruitment threshold of fast TMEM16F-/- motoneurons, TMEM16F loss of function induces motor defects during an effort.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to the selective death of motoneurons. Among the pathological processes already described, we know that motoneuronal excitability and calcium homeostasis are major features in ALS progression. Those are vulnerability factors which contribute to sequential degeneration starting with FF motoneurons and followed by FR motoneurons. Given the TMEM16F sensitivity to calcium and its involvement in regulating motoneuron excitability, we inhibited its expression in a SOD1G93A mouse model of ALS and conducted a longitudinal study. It highlights a gender-dependent protective effect of TMEM16F loss.
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Submitted on : Tuesday, September 3, 2019 - 9:39:07 AM
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  • HAL Id : tel-02276661, version 1



Claire Soulard. Rôle du canal chlorure activé par le calcium TMEM16F dans la motricité et implication dans la sclérose latérale amyotrophique. Sciences agricoles. Université Montpellier, 2019. Français. ⟨NNT : 2019MONTT008⟩. ⟨tel-02276661⟩



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