VesselCVO · A molecular and cellular mapping of the fenestrated vasculture of the circumventricular organs: from physiology to pathology.

In the brain, the blood vasculature harbours a unique specification: the Blood Brain Barrier (BBB), which restricts blood/brain exchanges to a select set of molecules. This particularity makes neurons blind to most peripheral signal. However, the peripheral organs and the brain have to communicate to maintain homeostasis and body functions such as metabolism, reproduction or growth. This dialog occurs in specific brain regions, the circumventricular organs (CVOs), characterized by a fenestrated vasculature allowing the free diffusion of blood-borne factors and secretion of neurohormones in the blood stream. Thus, CVOs are crucial for the periphery/brain dialog. Despite the apparent pivotal role of the fenestrated vasculature of the different CVOs in the blood/brain exchanges, little is known about their organisation, cellular composition and transcriptomic profile. Unlike the BBB vasculature, the fenestrated vasculature of the CVO is poorly described and the role of mural cells, known to support BBB vessel development and maintenance, in CVO remains undetermined. Equally unknown is how pathological contexts such as Alzheimer’s Disease (AD), showed to alter BBB vessels integrity and function, impact the CVO vasculature. In the VesselCVO project, we set out to fill in the void of information about the molecular and cellular anatomy of the CVO vasculature, the similarities and differences amongst CVOs and other fenestrated vasculature of the central nervous system, the relative role of mural cells present in these regions and translate this knowledge in the pathological context of Alzheimer’s Disease. These ambitious objectives will be achieved through the use of a multidisciplinary and complementary set of transcriptomic, bioinformatic, neuroanatomic and vascular biology approaches. This project will result in a better understanding of the brain's fenestrated vasculature, pivotal for its dialog with peripheral organs, in physiological and pathological contexts.