The proposed study will be devoted to observe and understand the regulatory mechanisms induced by prolonged and repeated adaptations to ground-based restraints simulating either microgravity (head-down tilts) or hypergravity (+Gz centrifugations). In both conditions of altered gravity, investigations will be performed with rats adapted to long periods of head-down tilt or centrifugation (15-30 days) interspaced with 30-day periods of readaptation to normal gravity. Using biospecimen-sharing programs, brains, hearts, kidneys, muscles and blood will be studied by the different NIS and INTAS teams, with the project to reinforce collaborative studies. Most of the investigations, to be performed by electron microscopy, immunocytoche-mistry, in situ hybridisation, biochemical and radioimmunological assays, will be dedicated to analyse the consequences of such environmental conditions on fluid, ionic and hormonal responses in structures involved in adaptation in either heart or kidney or brain. Numerous data elaborated in the last years have established and specified that neurosecretory nerve fibres in close association with specific glial cells show a variety of reactions to different stimuli.

Circumventricular organs involved in osmotic regulations in brain (e.g. neurohypophysis, median eminence, subfornical organ, organum vascularis of the lamina terminalis, choroid plexus, meningia), and hypothalamic nuclei responsible for production of osmoregulatory hormones will be therefore analysed to provide a necessary supplement of the intended project. Studies in the Central Nervous System (CNS) are aimed to understand structural and molecular mechanisms for adaptations occurring in motor control systems and systems involved in regulation of CSF production during exposures to altered gravity. Molecular mechanisms controlling formation, release and transport of synaptic vesicles at active zones will be performed to investigate functional changes at the level of single synapses. Quantitative parameters of animal limb muscle contractile apparatus and/or mitochondria (cross-sectional areas of muscle fibres, percent of slow and fast fibres, capillary/fibre ratio and capillary density, myofibrillar relative and absolute volume density) will be determined in heart and/or hindlimb muscles, after repetitive exposures to simulated microgravity and hypergravity.