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Hypoactivité, impesanteur et déconditionnement musculaire : étude des effets précoces chez l'homme dans un modèle d'immersion sèche

Abstract : For decades, one of the challenges of space science has been to assist the astronauts during their short or long term stay, mainly in orbital flights aboard a space station. In this context, our work contributes to the understanding of muscle deconditioning associated with a stay in weightlessness and to the evaluation of differents countermeasures.Whether in the space or health sector, scientists have had the opportunity to study the effects of chronic hypoactivity and weightlessness through various experimental models that are presented in Chapter 1. Part 1 also reviews the parameters of muscle deconditioning, which are mainly loss of mass and muscle strength. These two parameters appear early in a situation of hypoactivity and are not correlated with time, which results in a decrease in force of greater amplitude than the degrees of atrophy reported. Among the explanatory factors of this disproportion, the increased accumulation of fatty infiltrations and the denervation processes are explanatory elements and have also been the subject of our experiments.Our main objective is to characterize the early alterations of skeletal muscle using a model of dry immersion (DI). This model has been recognized for several years by Russian scientists to be more severe than extended bed rest and was set up a few years ago for the first time in Europe (Toulouse). The study consisted of placing 12 healthy male volunteers in dry immersion for 3 days. This first study in Europe allowed us to characterize the early changes of muscle deconditioning at the structural and functional level. The pre- and post-DI muscle biopsies, obtained from the Vastus Lateralis muscle, were used to quantify by immunohistology the degree of muscle atrophy by fiber type and to analyze the changes in myotypology. At the structural level, we reported by MRI a 10% decrease in the volume of the quadriceps, as well as a 10% atrophy, mainly attributed to type 1 fibers. From 3 days, the percentage of fibers expressing MyHC 1 also decreased, while the percentage of hybrid fiber increased (+ 1.3%). At the functional level, the loss of muscle strength is 11%, and we note an alteration of the viscoelastic properties of the rectus femoris. At the molecular level, we reported the changes of key proteins involved in protein balance regulation, for example, an early increase in the expression of the atrogene MURF1 (+ 41%) and a decrease expression of 4EBP1 (-17%). Transcriptomic analysis by RNA-seq also highlighted a significant expression change of 2872 genes.A second study allowed us to evaluate the effects of an anti-oxidant, anti-inflammatory cocktail as countermeasure during a hypoactivity experiments of 20 days and during a bed rest of 2 months. Pre- and post-DI and BR muscle biopsies were obtained from the Vastus Lateralis muscle and reported a degree of atrophy of about 20% in both protocols. The countermeasure has mainly shown a protective effect on type Iia fibers. Analysis of the E3 ligases MuRF-1 and Atrogin-1 did not indicate any modification in the two long-term protocols.The results of our short and long term studies of muscle deconditioning underline the rapid and early changes in the muscle system and highlight the need to study finely these initial changes and biomarkers of deconditioning, in order to optimize the effects of countermeasures over this initial period.
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Submitted on : Thursday, March 8, 2018 - 3:07:07 PM
Last modification on : Thursday, July 2, 2020 - 2:00:33 PM
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Rémi Demangel. Hypoactivité, impesanteur et déconditionnement musculaire : étude des effets précoces chez l'homme dans un modèle d'immersion sèche. Médecine humaine et pathologie. Université Montpellier, 2017. Français. ⟨NNT : 2017MONT4008⟩. ⟨tel-01726701⟩



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