Descrizione del progetto
Il ruolo delle cellule gliali note come taniciti nell’invecchiamento sano
La sopravvivenza degli organismi dipende dall’omeostasi energetica e implica il controllo delle funzioni neuroendocrine che integrano il feedback metabolico. I taniciti sono cellule gliali che rivestono il pavimento del terzo ventricolo nell’eminenza mediana dell’ipotalamo, e controllano la secrezione di neuropeptidi da parte di neuroni ipotalamici nella circolazione portale pituitaria e regolano lo scambio di fluidi tra sangue e cervello e sangue e fluido cerebrospinale. I taniciti trasportano attivamente i segnali metabolici ai neuroni ipotalamici che controllano l’assunzione di alimenti. L’obiettivo del progetto WATCH, finanziato dall’UE, consiste nell’impiegare tecnologie d’avanguardia nella neuroscienza dei sistemi, nella genetica murina e nella ricerca transnazionale per chiarire il ruolo dei taniciti e fornire nuove direzioni nella ricerca dei biomarcatori e in approcci terapeutici per una serie di disturbi che compromettono l’invecchiamento sano.
Obiettivo
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.
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Meccanismo di finanziamento
ERC-SyG - Synergy grantIstituzione ospitante
75654 Paris
Francia