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.
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.