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Well-Aging and the Tanycytic Control of Health

Project description

Role of glial cells tanycytes in healthy ageing

The organisms' survival depends on energy homeostasis, involving the control of neuroendocrine functions that integrate metabolic feedback. Tanycytes are glial cells lining the floor of the third ventricle in the median eminence of the hypothalamus which control the secretion of neuropeptides by hypothalamic neurons into the pituitary portal circulation and regulate blood-brain and blood-cerebrospinal fluid exchanges. Tanycytes actively shuttle metabolic signals to hypothalamic neurons that control food intake. The goal of the EU-funded WATCH project is to employ state-of-the-art technologies in systems neuroscience, mouse genetics, and translational research, to elucidate the role of tanycytes and provide new directions in biomarker research and therapeutic approaches for a variety of disorders that impair healthy ageing.

Objective

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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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-SyG - Synergy grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2018-SyG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 4 243 750,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 4 493 750,00

Beneficiaries (4)

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