Projektbeschreibung
Was die Gliazellen Tanycyten mit dem gesunden Altern zu tun haben
Organismen brauchen zum Überleben die Energiehomöostase. Daran sind neuroendokrine Funktionen beteiligt, die Feedback aus dem Stoffwechsel einbeziehen. Tanycyten sind Gliazellen, die den Boden des dritten Ventrikels in der Eminentia mediana des Hypothalamus auskleiden. Sie kontrollieren die Abgabe von Neuropeptiden aus den Nervenzellen im Hypothalamus in den Blutstrom der Hypophysenpfortader und steuern den Austausch zwischen Hirn und Blut bzw. zwischen Blut und Liquor. Die Tanycyten transportieren aktiv Stoffwechselsignale zu den Nervenzellen im Hypothalamus, die die Nahrungsaufnahme steuern. Mithilfe von neuesten Technologien der systemischen Neurowissenschaften, Mausgenetik und translationaler Forschung will das EU-finanzierte Projekt WATCH die Rolle der Tanycyten entschlüsseln. Gleichzeitig sollen neue Wege in der Biomarkerforschung aufgezeigt und therapeutische Ansätze für eine Vielzahl von Fehlfunktionen angeregt werden, die einem gesunden Altern entgegenstehen.
Ziel
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.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-SyG - Synergy grantGastgebende Einrichtung
75654 Paris
Frankreich