Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

OBJECTIVES : The proposed research program will explore the role of hypothalamic tanycytes.
BACKGROUND & RATIONALE : Tanycytes are specialized ependymal cells found in a few confined hypothalamic areas which lack a complete blood brain barrier (BBB). Tanycyte cell bodies form the ventricular floor in the BBB-lacking areas, and their processes extend deep into the brain parenchyma, contacting fenestrated vasculature, and thus are exposed to the peripheral circulation. The function of tanycytes is poorly understood; however, given their strategic location, bridging between the general circulation and the central nerve system, these cells might play an important role in transmitting signals between the circulation and the brain.
Our recent work has revealed the presence of a large population of tanycytes in organum vasculosum of lamina terminalis (OVLT). OVLT is one of the most important BBB-lacking sensory areas providing the brain with the information from the periphery and contributing to the generation of centrally-mediated physiological responses. Our data show that OVLT tanycytes create a dense network tightly embedding local neurons. Although the tanycytes constitute a prevalent population in this vital brain region, their function remains elusive.
AIMS & METHODS:
1 . Studying the role of OVLT tanycytes in detecting blood-borne circulating signals to modify the activity of neurons. To selectively target tanycytes, we will manipulate the levels and activity of vimentin (a major structural component of tanycytes) with genetic (tamoxifen-inducible Vimentin-Cre mouse line) and pharmacological tools, and will modulate the expression of membrane receptors and transporters in tanycytes by conditional knockout and/or overexpression using adeno-associated virus. These approaches will be combined with functional analysis of tanycyte activity using electrophysiology and calcium imaging in vitro and in vivo .
2 . Investigating the structural organization of OVLT tanycytes. We will characterize tanycyte morphology and organization, and their contacts with neurons and vasculature using superresolution imaging.
3 . Studying the stem cell potential of OVLT tanycytes. We will assess the stem cell potential of OVLT tanycytes using markers for different lineages, performing long-term tanycyte lineage tracing in vivo using tamoxifen-inducible Nestin-Cre mice, and studying the neurogenesis by examining neurospherogenic potential of OVLT tanycytes and evaluating the functionality of newborn neurons using electrophysiology.
OUTCOME : The proposed work will explore the function of previously undescribed cell population in the vital brain area which serves as an interface between the peripheral circulation and the central nervous system. Deciphering the role of tanycytes in this area will provide new insights into one of the least-explored corners of the mammalian brain.