Adaptation à l’hypergravité au cours du développement de la souris – AdapHyG

This project wants to understand the role of gravity as a factor conditioning the mammalian development. We want to describe the cellular and molecular mechanisms modified by gravity and implicated in the mammalian physiology during maturation process. This study wants to characterize the effects of direction and intensity of gravity on physiological functions (dose-effect, reversion'). To do that, we change the intensity of gravity applied on mice during their development by centrifugation. This project coordinates several laboratories. Each laboratory is a specialist in the study of one physiological function. The consortium assembles these teams to organize and correlate physiological parameters. This program is possible because the CNES gives us the centrifuged mouse living system. This project is composed by several studies on the determination of the critical periods in organism adaptation to gravity. Firstly, it is necessary to obtain mouse reproduction in centrifuge in good condition (parameters like stress, and direct effect of centrifugation of adult mice should be measured). Afterwards, the influence of vestibular stimulation by hypergravity, vestibular ablation, and hormonal modifications will be investigated on bone, muscle and vessels. These results will be compared to those measured after low frequency mechanical stimulations (the same that used in sport protocols). The effect of modified gravity will be investigated on induced immune response (antibody production after immunisation) or acquired immune response (immunoglobulin gene reorganisation) and on autonomous nervous system. At last, we will study how hypergravity-induced developmental modifications will be maintained during adult life. In this particular case of the gravity influence study, we want to participate to elucidate the question of the influence of epigenetic factor on gene expression in several physiological functions. This project will also participate to health questions; in fact, we want to determinate the mechanisms of adaptation to modified gravity and readaptation of Earth gravity level. If this last point seems essential to space medicine, it also essential to ordinary medicine because these mechanisms are probably also implicated in physiological adaptation to environmental stress as mechanical stress applied in sport, or work. For this reason, our proposal is also the basis of functional adaptation protocols.