Tanycytic VEGF receptor signaling in the blood-hypothalamus barrier: a new player in the communication between the brain and the periphery

Ines Martinez-Corral, Emilie Caron, Sreekala Nampoothiri, Vincent Prevot  

Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine brain, Lille Neuroscience and cognition, UMR-S1172, Lille France.  

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Abstract Text
The communication between the brain and the periphery is tightly regulated by the blood brain barrier  (BBB),  in  which  endothelial  cells,  sealed  by  tight  junctions,  and perivascular  cells contribute  forming  the  neurovascular  unit. However,  specific  brain  regions  known as circumventricular organs (CVOs) lack this type of barrier. CVOs are characterized by the presence  of  fenestrated  vascularization  and  the  translocation  of  barrier  properties  to non-endothelial cells.

Among CVOs, the median eminence (ME) is located in the base of the hypothalamus, ventral to the third ventricle and adjacent to  the arcuate nucleus (ARH). The ME is a key interface between  the  neural  and  endocrine  systems  involved  in  the hypothalamic  control  of  energy homeostasis. The presence of a fenestrated endothelium in the ME allows the passive diffusion of blood-borne  molecules  into  the  parenchyma  and  vice-versa. However,  the  passage  of molecules beyond the ME to the ARH or cerebrospinal fluid is tightly regulated by tanycytes. These specialized ependymoglial cells that line the wall of the third ventricle are sealed by tight junctions, forming the blood hypothalamus barrier. Tanycytes send long processes to contact the wall of the fenestrated vessels in the ME, but also of the BBB vessels in the ARH.

In the ME as elsewhere, VEGFR signaling is not specific to blood vessels. Using different approaches, we have observed that a subset of tanycytes expresses VEGFR2, and that in mice, tanycytic VEGFR2 signaling is involved in the maintenance of body homeostasis. A potential role in metabolic diseases such as obesity is also being explored.

Altogether, our results suggest that within tanycytes, vascular-specific pathways are directly involved in the communication between hypothalamus and vasculature, and ultimately between brain and periphery.