GHRELIN TRANSPORT ACROSS THE BLOOD-CEREBROSPINAL FLUID BARRIER OCCURS IN A GHRELIN RECEPTOR INDEPENDENT-MANNER

MAIA URIARTE; MONIDA IBERNON; DANIEL CASTROGIOVANNI; MARIO PERELLO; NICOLAS DE FRANCESCO; VINCENT PREVOT

Congreso; 10th World Congress of Neuroscience, IBRO; 2019

IBRO

Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via a G-protein coupled receptor, named growth hormone secretagogue receptor (GHSR), which is highly expressed in the pituitary and the brain. Studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier (BCSFB) an interface constituted by the choroid plexus and the hypothalamic tanycytes. Here, we used in vivo, ex vivo and in vitro strategies to investigate whether GHSR is necessary for the transport of ghrelin through the BCSFB. In vivo, we found that exogenously administered fluorescent-ghrelin is detected in the epithelial cells of the choroid plexus and in tanycytes of both wild type and GHSR-deficient mice, and that systemically administered ghrelin is found in the CSF of both groups of mice. Also, we were able to measure an endogenous rise of ghrelin levels in the CSF of both groups of mice exposed to a caloric restriction protocol. Additionally, we found that both the choroid plexus and the tanycytes display fluorescent-ghrelin uptake ex vivo and in vitro, respectively. Finally, we found that the expression of GHSR mRNA was detectable in the choroid plexus of wild type mice, but undetectable in hypothalamic tanycytes. Thus, our results suggest that the cells of the BSCFB are able to internalize ghrelin via a GHSR-independent mechanism.