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Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms

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  • Maia Uriarte, Universidad Nacional de La Plata
  • ,
  • Pablo N. De Francesco, Universidad Nacional de La Plata
  • ,
  • Gimena Fernández, Universidad Nacional de La Plata
  • ,
  • Daniel Castrogiovanni, Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)]
  • ,
  • Micaela D'Arcangelo, Universidad Nacional de La Plata
  • ,
  • Mónica Imbernon, Université de Lille
  • ,
  • Sonia Cantel, Universite de Montpellier
  • ,
  • Severine Denoyelle, Universite de Montpellier
  • ,
  • Jean Alain Fehrentz, Universite de Montpellier
  • ,
  • Jeppe Praetorius
  • Vincent Prevot, Université de Lille
  • ,
  • Mario Perello, Universidad Nacional de La Plata

Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via the growth hormone secretagogue receptor (GHSR), which is highly expressed in the brain. Strikingly, the accessibility of ghrelin to the brain seems to be limited and restricted to few brain areas. Previous studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier, an interface constituted by the choroid plexus and the hypothalamic tanycytes. Here, we performed a variety of in vivo and in vitro studies to test the hypothesis that the transport of ghrelin across the blood-CSF barrier occurs in a GHSR-dependent manner. In vivo, we found that the uptake of systemically administered fluorescent ghrelin in the choroid plexus epithelial (CPE) cells and in hypothalamic tanycytes depends on the presence of GHSR. Also, we detected lower levels of CSF ghrelin after a systemic ghrelin injection in GHSR-deficient mice, as compared to WT mice. In vitro, the internalization of fluorescent ghrelin was reduced in explants of choroid plexus from GHSR-deficient mice, and unaffected in primary cultures of hypothalamic tanycytes derived from GHSR-deficient mice. Finally, we found that the GHSR mRNA is detected in a pool of CPE cells, but is nearly undetectable in hypothalamic tanycytes with current approaches. Thus, our results suggest that circulating ghrelin crosses the blood-CSF barrier mainly by a mechanism that involves the GHSR, and also possibly via a GHSR-independent mechanism.

Original languageEnglish
Article number111449
JournalMolecular and Cellular Endocrinology
Volume538
Number of pages12
ISSN0303-7207
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier B.V.

    Research areas

  • Choroid plexus, Ependymal cells, Ghrelin, Tanycytes

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