Main topic: Study of blood-brain interfaces in contributing to the delivery of blood-borne molecules to their neuronal targets.
The blood-brain interfaces are the structures through which the peripheral organs and the central nervous system communicate to regulate body homeostasis. Our works focus on the role of circumventricular organs (CVOs) in contributing to the delivery of blood-borne molecules to their neuronal targets.
We have shown that tanycytes and fenestrated vessels, the two main features of CVOs, form a blood-brain interface that regulates the diffusion of blood-borne molecules into the cerebrospinal fluid and the rest of the brain while allowing their free diffusion into the parenchyma of the CVOs (Figure) (Mullier et al., 2010, Langlet et al., 2013a). Moreover this “brain window” can be extended to CVO surrounding parenchyma as shown for the hypothalamic arcuate nucleus (ARC) that adjoins the median eminence (ME) (Langlet et al., 2013b). After fasting for 24h, a number of the blood-brain-barrier capillaries of the arcuate nucleus became fenestrated, resulting in the barrier properties becoming delocalized to the tanycytes they are in contact with. We showed that fasting-induced increased capillary permeability enhanced the penetration and action of circulating metabolic signals on ARH neurons. These results highlight a new concept in the way the energy balance can be regulated: via the plasticity of the circumventricular organ interfaces. They emphasize the role of the CVOs in contributing to the delivery of blood-borne molecules conveying metabolic information to the sensory neurons whilst ensuring brain homeostasis.
Extension of the median eminence features to the arcuate nucleus to improved access of metabolic substrates to their neuronal targets.
A: Localization of the mediobasal hypothalamus comprising the median eminence (ME) and the arcuate nucleus (ARC). B: In contrast to the blood brain barrier (BBB), vessels of the ME harbour a fenestrated endothelium and lack tight junction complexes. Barrier properties are shifted from the vasculature to the ventricular wall formed by specialized CVO ependymal cells called tanycytes. This displacement allows the diffusion of blood-borne molecules into the parenchyma of the CVOs (blue) while the tanycyte barrier controls their free diffusion into the cerebrospinal fluid. C: During fasting the ME “brain window” extends to the ARC, resulting in the improved access of metabolic substrates to this nucleus (blue and arrow). Indeed, while capillary fenestrations are restricted to the ME in fed animals, fasting promotes the fenestration of capillaries reaching the ARH. Simultaneously, the tanycyte barrier extends up the ependymal layer to the region bordering the ARH.
1. Langlet F, Mullier A, Bouret SG, Prevot V, Dehouck B (2013a). Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain. J Comp Neurol 521, 3389-3405.
2. Langlet F, Levin BE, Luquet S, Mazzone M, Messina A, Dunn-Meynell AA, Balland E, Lacombe A, Mazur D, Carmeliet P, Bouret SG, Prevot V, Dehouck B (2013b). Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab 17(4):607-617.
3. Mullier A, Bouret SG, Prevot V, Dehouck B (2010). Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain. J Comp Neurol 518, 943-962.