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Well-Aging and the Tanycytic Control of Health

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.

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /natural sciences/biological sciences/genetics and heredity
  • /natural sciences/biological sciences/neurobiology
  • /natural sciences/biological sciences/neurobiology/neuroscience

Call for proposal

ERC-2018-SyG
See other projects for this call

Funding Scheme

ERC-SyG - Synergy grant

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 4 493 750

Beneficiaries (3)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 4 493 750
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
UNIVERSITAET zu LUEBECK
Germany
EU contribution
€ 2 875 000
Address
Ratzeburger Allee 160
23562 Lubeck
Activity type
Higher or Secondary Education Establishments
UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Spain
EU contribution
€ 2 497 500
Address
Colexio De San Xerome Praza Do Obradoiro S/n
15782 Santiago De Compostela
Activity type
Higher or Secondary Education Establishments