The Blood-Cerebrospinal Fluid Barrier Transports Circulating Ghrelin Into The Brain

URIARTE, MAIA; DE FRANCESCO, PABLO NICOLÁS; FERNÁNDEZ, GIMENA; CABRAL, AGUSTINA; CASTROGIOVANNI, DANIEL; PERELLÓ, MARIO

Córdoba, Argentina

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

Sociedad Argentina de Investigación en Neurociencias

Ghrelin is a 28-amino acid hormone secretedfrom the stomach which mainly acts in the brain to regulate food intake andneuroendocrine axes. However, the accessibility of circulating ghrelin to thebrain is restricted, with no conclusive evidence of it crossing the blood-brainbarrier (BBB). In this study, we hypothesized that ghrelin can reach its brainnuclei targets by crossing the blood-cerebrospinal fluid barrier (BCSFB), whichis composed of the ependymal cells of the choroid plexus and the hypothalamictanycytes. 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-injectedF-ghrelin reached the median eminence and the ventromedial arcuate nucleus atearly time points, while, at later time points F-ghrelin was found in thecerebrospinal fluid (CSF) as well as in brain parenchyma in close apposition tothe dorsal wall of the third ventricle. Additionally, we found that centralinjections of either an anti-ghrelin antibody, which immuno-neutralizes CSFghrelin, or a scrambled version of F-ghrelin, which was also found to beinternalized by the cells of the BCSFB, partially impairs food intake andneuronal activation promoted by peripheral ghrelin. We thus conclude that thecells of the BCSFB can transport ghrelin from the circulation into the CSF andthe brain parenchyma.