The blood-cerebrospinal fluid (CSF) barrier transports circulating ghrelin into the brain

URIARTE, MAIA; PERELLO, MARIO; DE FRANCESCO, PABLO NICOLÁS; FERNANDEZ, GIMENA

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Ghrelin is a 28-amino acid hormone secreted from thestomach which mainly acts in the brain to regulate foodintake and neuroendocrine axes. However, the accessibilityof circulating ghrelin to the brain is restricted, with no conclusive evidence of it crossing the blood?brain barrier. In thisstudy, we hypothesized that ghrelin can reach its brain nucleitargets by crossing the blood?cerebrospinal fluid barrier(BCSFB), which is composed of the ependymal cells of thechoroid 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 internalizeghrelin. Also, in time-response studies, we found that systemically injected F-ghrelin reached the median eminenceand 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 closeapposition to the dorsal wall of the third ventricle.Additionally, we found that central injections of either ananti-ghrelin antibody, which immuno-neutralizes CSF ghrelin,or a scrambled version of F-ghrelin, which was also found tobe internalized by the cells of the BCSFB, partially impairsfood intake and neuronal activation promoted by peripheralghrelin. We thus conclude that the cells of the BCSFB cantransport ghrelin from the circulation into the CSF and thebrain parenchyma.