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

Autor: Uriarte M; Laboratory of Neurophysiology, [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata, Argentina., De Francesco PN; Laboratory of Neurophysiology, [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata, Argentina., Fernández G; Laboratory of Neurophysiology, [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata, Argentina., Castrogiovanni D; Cell Culture Facility of the Multidisciplinary Institute of Cell Biology [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata, Argentina., D'Arcangelo M; Laboratory of Neurophysiology, [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata, Argentina., Imbernon M; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience and Cognition, UMR, S1172, Lille, France., Cantel S; Institut des Biomolécules Max Mousseron, UMR, 5247, CNRS-Université Montpellier-ENSCM, Faculté de Pharmacie, Montpellier, France., Denoyelle S; Institut des Biomolécules Max Mousseron, UMR, 5247, CNRS-Université Montpellier-ENSCM, Faculté de Pharmacie, Montpellier, France., Fehrentz JA; Institut des Biomolécules Max Mousseron, UMR, 5247, CNRS-Université Montpellier-ENSCM, Faculté de Pharmacie, Montpellier, France., Praetorius J; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Prevot V; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience and Cognition, UMR, S1172, Lille, France., Perello M; Laboratory of Neurophysiology, [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata, Argentina. Electronic address: mperello@imbice.gov.ar.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2021 Dec 01; Vol. 538, pp. 111449. Date of Electronic Publication: 2021 Aug 31.
DOI: 10.1016/j.mce.2021.111449
Abstrakt: 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.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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