Tanycyte‐like cells form a blood–cerebrospinal fluid barrier in the circumventricular organs of the mouse brain

Abstract

Tanycytes are highly specialized ependymal cells that form a blood–cerebrospinal fluid (CSF) barrier at the level of the median eminence (ME), a circumventricular organ (CVO) located in the tuberal region of the hypothalamus. This ependymal layer harbors well-organized tight junctions, a hallmark of central nervous system barriers that is lacking in the fenestrated portal vessels of the ME. The displacement of barrier properties from the vascular to the ventricular side allows the diffusion of blood-borne molecules into the parenchyma of the ME while tanycyte tight junctions control their diffusion into the CSF, thus maintaining brain homeostasis. In the present work, we combined immunohistochemical and permeability studies to investigate the presence of tanycyte barriers along the ventricular walls of other brain CVOs. Our data indicate that, unlike cuboidal ependymal cells, ependymal cells bordering the CVOs possess long processes that project into the parenchyma of the CVOs to reach the fenestrated capillary network. Remarkably, these tanycyte-like cells display well-organized tight junctions around their cell bodies. Consistent with these observations, permeability studies show that this ependymal layer acts as a diffusion barrier. Together, our results suggest that tanycytes are a characteristic feature of all CVOs and yield potential new insights into their involvement in regulating the exchange between the blood, the brain, and the CSF within these “brain windows.”

Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior

“…This is because tanycytes link the ventricular and vascular compartments, forming a blood/CSF interface in the tubal region of the hypothalamus (Langlet et al, 2013). β2‐tanycytes have long processes that extend to the perivascular space of the capillary network of the ME to reach the fenestrated capillary network.…”

“…Their apical poles contact the cerebrospinal fluid (CSF), and basal extensions project into the arcuate nucleus (AN) (Flament‐Durand & Brion, 1985). Tanycytes are classified into four main groups on the basis of differences in their anatomical localization and gene expression: α1, α2 (Robins et al, 2013), β1, and β2 (Elizondo‐Vega et al, 2015; Langlet, Mullier, Bouret, Prevot, & Dehouck, 2013). β2‐tanycytes cover the floor of the 3V; in their apical face, they present tight junctions that form the CSF‐median eminence (ME) barrier and extend their projections inside the ME.…”

“…β2‐tanycytes cover the floor of the 3V; in their apical face, they present tight junctions that form the CSF‐median eminence (ME) barrier and extend their projections inside the ME. Interestingly, these tight junctions and cellular contacts can change, depending on the metabolic state of the organism (Langlet et al, 2013). Furthermore, GLUT2‐positive α2‐ and β1‐tanycytes are located in the lateral walls of the 3V and make contact with orexigenic AN neurons, which produce neuropeptide Y (NPY) and agouti‐related protein (AGRP), and anorexigenic AN neurons, which produce proopiomelanocortin (POMC) and the cocaine‐amphetamine‐regulated transcript (CART), through their extensive processes (Broberger, Johansen, Johansson, Schalling, & Hokfelt, 1998; Elias et al, 1998; Kristensen et al, 1998).…”

Localization of Tight Junctions Between Tanycyte-Like Cells of the Sulcus Medianus Organum in Rat Brain

“…These proteins are the ZO1, occludin, and claudin1. ZO1 and occludin immunolabeling was detected at the cells that line the 3rd ventricle and the AP of the 4 th ventricle, in other words, those specialized ECs forming the ventricular walls of the CVOs (25) . Since these CVOs lack an endothelial BBB, they serve neurohemal or neurosecretory functions.…”

“…Most literatures investigate the caudal part of the SM where the AP is framed by processbearing ECs that connect the ventricular and fenestrated vessels compartments, as portrayed in the ME (25) . Researchers, however, did not elaborate on the rostral part of the SM where little attention is paid for the presence of the SMO as one of the CVOs.…”