The blood-cerebrospinal fluid barrier transports circulating ghrelin into the brain.

MAIA URIARTE; PABLO N. DE FRANCESCO; GIMENA FERNANDEZ; AGUSTINA CABRAL; DANIEL CASTROGIOVANNI; MARIO PERELLÓ

Congreso; XXXIII Congreso Anual SAN 2018; 2018

Ghrelin is a 28-amino acid hormone secreted from the stomach which mainly acts in the brain to regulate food intake and neuroendocrine axes. However, the accessibility of circulating ghrelin to the brain is restricted, with no conclusive evidence of it crossing the blood-brain barrier (BBB). In this study, we hypothesized that ghrelin can reach its brain nuclei targets by crossing the blood-cerebrospinal fluid barrier (BCSFB), which is composed of the ependymal cells of the choroid plexus and the hypothalamic tanycytes. Using systemic injections of a fluorescent ghrelin tracer (F-ghrelin), we found that the cells of the BCSFB were able to internalize ghrelin. Also, in time-response studies we found that systemically-injected F-ghrelin reached the median eminence and the ventromedial arcuate nucleus at early time points, while, at later time points F-ghrelin was found in the cerebrospinal fluid (CSF) as well as in brain parenchyma in close apposition to the dorsal wall of the third ventricle. Additionally, we found that central injections of either an anti-ghrelin antibody, which immuno-neutralizes CSF ghrelin, or a scrambled version of F-ghrelin, which was also found to be internalized by the cells of the BCSFB, partially impairs food intake and neuronal activation promoted by peripheral ghrelin. We thus conclude that the cells of the BCSFB can transport ghrelin from the circulation into the CSF and the brain parenchyma.