Descripción del proyecto
La función de las células ependimarias de los neurogliocitos en el envejecimiento saludable
La supervivencia de los organismos depende de la homeostasis energética, que implica el control de funciones neuroendocrinas que integran la retroalimentación metabólica. Las células ependimarias son neurogliocitos que recubren el piso del tercer ventrículo en la protuberancia media del hipotálamo y que controlan la secreción de neuropéptidos por las neuronas hipotalámicas en la circulación portal pituitaria y regulan los intercambios hematoencefálicos y hematocefalorraquídeos. Las células ependimarias transmiten activamente señales metabolómicas a las neuronas hipotalámicas que controlan la ingesta de alimentos. El proyecto WATCH, financiado con fondos europeos, se propone emplear tecnologías vanguardistas de neurociencia de sistemas, genética murina e investigación traslacional para determinar la función de las células ependimarias y ofrecer nuevas posibilidades en la investigación de biomarcadores y métodos terapéuticos para una variedad de enfermedades que afectan el envejecimiento saludable.
Objetivo
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.
Ámbito científico
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Régimen de financiación
ERC-SyG - Synergy grantInstitución de acogida
75654 Paris
Francia