Description du projet
Le rôle des tanycytes des cellules gliales dans le vieillissement en bonne santé
La survie des organismes dépend de l’homéostasie énergétique, impliquant le contrôle des fonctions neuroendocriniennes qui inclut un feedback métabolique. Les tanycytes sont des cellules gliales tapissant le plancher du troisième ventricule dans l’éminence médiane de l’hypothalamus, elles contrôlent la sécrétion de neuropeptides par les neurones hypothalamiques dans la circulation de la porte hypophysaire et régulent les échanges sang-cerveau et sang-fluide céphalo-rachidien. Les tanycytes font activement la navette entre les signaux métaboliques et les neurones hypothalamiques qui contrôlent la prise de nourriture. L’objectif du projet WATCH, financé par l’UE, est d’utiliser des technologies de pointe en neuroscience des systèmes, en génétique de la souris et en recherche translationnelle, afin d’élucider le rôle des tanycytes et de fournir de nouvelles orientations dans la recherche de biomarqueurs et d’approches thérapeutiques pour toute une série de troubles qui nuisent au vieillissement en bonne santé.
Objectif
The survival of an organism depends on energy homeostasis, involving the control of neuroendocrine functions that integrate metabolic feedback and adapt the response of the organism to physiological demands. Tanycytes, specialized glial cells lining the floor of the third ventricle in the median eminence of the hypothalamus, act as linchpins of these processes, dynamically controlling the secretion of neuropeptides by hypothalamic neurons into the pituitary portal circulation and regulating blood-brain and blood-cerebrospinal fluid exchanges, both processes that depend on their morphological plasticity in response to the physiological state. In addition to their barrier properties, they actively shuttle circulating metabolic signals to hypothalamic neurons that control food intake. The overarching goal of WATCH is to synergistically employ state-of-the-art technologies in systems neuroscience, mouse genetics and bench-to-bedside research, to explore the role of these unique and versatile cells, providing new directions in biomarker research and new therapeutic approaches for a variety of disorders that impair well-aging. Our specific aims are:
1. Genetic dissection of the in vivo regulation, pathophysiological function and molecular markers of tanycytes classified according to their anatomical location.
2. Identification of novel heterogeneous, molecularly distinct tanycytes and associated endothelial cells and determining how these characteristics evolve under distinct physiological and pathological conditions.
3. Functional validation of newly classified subgroups of tanycytes and the specific modulation of the activity of these subgroups at the experimental level.
4. Exploration of the functional consequences of pharmacologically activating pathways required for the tanycytic shuttling of metabolic signals on their CSF levels of these factors, hypothalamic activity and cognition in animal models and patients with morbid obesity or age-related cognitive deficits.
Champ scientifique
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Régime de financement
ERC-SyG - Synergy grantInstitution d’accueil
75654 Paris
France