Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain

Autores
Uriarte Donati, Maia; De Francesco, Pablo Nicolás; Fernández, Gimena; Cabral, Agustina Soledad; Castrogiovanni, Daniel Cayetano; Lalonde, Tyler; Luyt, Leonard G.; Trejo, Sebastián Alejandro; Perelló, Mario Carlos
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice have shown that the accessibility of ghrelin into the brain is limited and that it mainly takes place in some circumventricular organs, such as the median eminence. Notably, some known brain targets of ghrelin are distantly located from the circumventricular organs. Thus, we hypothesized that ghrelin could also access the brain via the blood-cerebrospinal fluid (CSF) barrier, which consists of the choroid plexus and the hypothalamic tanycytes. Using systemic injection of ghrelin or fluorescent-ghrelin in mice, we found that cells of the blood-CSF barrier internalize these molecules. In time-response studies, we found that peripherally injected fluorescent-ghrelin quickly reaches hypothalamic regions located in apposition to the median eminence and more slowly reaches the periventricular hypothalamic parenchyma, adjacent to the dorsal part of the third ventricle. Additionally, we found that CSF ghrelin levels increase after the systemic administration of ghrelin, and that central infusions of either an anti-ghrelin antibody, which immuno-neutralizes CSF ghrelin, or a scrambled version of ghrelin, which is also internalized by cells of the blood-CSF barrier, partially impair the orexigenic effect of peripherally injected ghrelin. Thus, current evidence suggests that the blood-CSF barrier can transport circulating ghrelin into the brain, and that the access of ghrelin into the CSF is required for its full orexigenic effect.
Instituto Multidisciplinario de Biología Celular
Materia
Biología
Ependymal cells
Choroid plexus
Tanycytes
Hypothalamus
Ghrelin
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/145491

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network_name_str SEDICI (UNLP)
spelling Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brainUriarte Donati, MaiaDe Francesco, Pablo NicolásFernández, GimenaCabral, Agustina SoledadCastrogiovanni, Daniel CayetanoLalonde, TylerLuyt, Leonard G.Trejo, Sebastián AlejandroPerelló, Mario CarlosBiologíaEpendymal cellsChoroid plexusTanycytesHypothalamusGhrelinThe stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice have shown that the accessibility of ghrelin into the brain is limited and that it mainly takes place in some circumventricular organs, such as the median eminence. Notably, some known brain targets of ghrelin are distantly located from the circumventricular organs. Thus, we hypothesized that ghrelin could also access the brain via the blood-cerebrospinal fluid (CSF) barrier, which consists of the choroid plexus and the hypothalamic tanycytes. Using systemic injection of ghrelin or fluorescent-ghrelin in mice, we found that cells of the blood-CSF barrier internalize these molecules. In time-response studies, we found that peripherally injected fluorescent-ghrelin quickly reaches hypothalamic regions located in apposition to the median eminence and more slowly reaches the periventricular hypothalamic parenchyma, adjacent to the dorsal part of the third ventricle. Additionally, we found that CSF ghrelin levels increase after the systemic administration of ghrelin, and that central infusions of either an anti-ghrelin antibody, which immuno-neutralizes CSF ghrelin, or a scrambled version of ghrelin, which is also internalized by cells of the blood-CSF barrier, partially impair the orexigenic effect of peripherally injected ghrelin. Thus, current evidence suggests that the blood-CSF barrier can transport circulating ghrelin into the brain, and that the access of ghrelin into the CSF is required for its full orexigenic effect.Instituto Multidisciplinario de Biología Celular2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf4120-4134http://sedici.unlp.edu.ar/handle/10915/145491enginfo:eu-repo/semantics/altIdentifier/issn/1559-1182info:eu-repo/semantics/altIdentifier/issn/0893-7648info:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-018-1362-8info:eu-repo/semantics/altIdentifier/pmid/30276663info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:32:27Zoai:sedici.unlp.edu.ar:10915/145491Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:32:28.216SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
title Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
spellingShingle Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
Uriarte Donati, Maia
Biología
Ependymal cells
Choroid plexus
Tanycytes
Hypothalamus
Ghrelin
title_short Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
title_full Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
title_fullStr Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
title_full_unstemmed Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
title_sort Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain
dc.creator.none.fl_str_mv Uriarte Donati, Maia
De Francesco, Pablo Nicolás
Fernández, Gimena
Cabral, Agustina Soledad
Castrogiovanni, Daniel Cayetano
Lalonde, Tyler
Luyt, Leonard G.
Trejo, Sebastián Alejandro
Perelló, Mario Carlos
author Uriarte Donati, Maia
author_facet Uriarte Donati, Maia
De Francesco, Pablo Nicolás
Fernández, Gimena
Cabral, Agustina Soledad
Castrogiovanni, Daniel Cayetano
Lalonde, Tyler
Luyt, Leonard G.
Trejo, Sebastián Alejandro
Perelló, Mario Carlos
author_role author
author2 De Francesco, Pablo Nicolás
Fernández, Gimena
Cabral, Agustina Soledad
Castrogiovanni, Daniel Cayetano
Lalonde, Tyler
Luyt, Leonard G.
Trejo, Sebastián Alejandro
Perelló, Mario Carlos
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología
Ependymal cells
Choroid plexus
Tanycytes
Hypothalamus
Ghrelin
topic Biología
Ependymal cells
Choroid plexus
Tanycytes
Hypothalamus
Ghrelin
dc.description.none.fl_txt_mv The stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice have shown that the accessibility of ghrelin into the brain is limited and that it mainly takes place in some circumventricular organs, such as the median eminence. Notably, some known brain targets of ghrelin are distantly located from the circumventricular organs. Thus, we hypothesized that ghrelin could also access the brain via the blood-cerebrospinal fluid (CSF) barrier, which consists of the choroid plexus and the hypothalamic tanycytes. Using systemic injection of ghrelin or fluorescent-ghrelin in mice, we found that cells of the blood-CSF barrier internalize these molecules. In time-response studies, we found that peripherally injected fluorescent-ghrelin quickly reaches hypothalamic regions located in apposition to the median eminence and more slowly reaches the periventricular hypothalamic parenchyma, adjacent to the dorsal part of the third ventricle. Additionally, we found that CSF ghrelin levels increase after the systemic administration of ghrelin, and that central infusions of either an anti-ghrelin antibody, which immuno-neutralizes CSF ghrelin, or a scrambled version of ghrelin, which is also internalized by cells of the blood-CSF barrier, partially impair the orexigenic effect of peripherally injected ghrelin. Thus, current evidence suggests that the blood-CSF barrier can transport circulating ghrelin into the brain, and that the access of ghrelin into the CSF is required for its full orexigenic effect.
Instituto Multidisciplinario de Biología Celular
description The stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice have shown that the accessibility of ghrelin into the brain is limited and that it mainly takes place in some circumventricular organs, such as the median eminence. Notably, some known brain targets of ghrelin are distantly located from the circumventricular organs. Thus, we hypothesized that ghrelin could also access the brain via the blood-cerebrospinal fluid (CSF) barrier, which consists of the choroid plexus and the hypothalamic tanycytes. Using systemic injection of ghrelin or fluorescent-ghrelin in mice, we found that cells of the blood-CSF barrier internalize these molecules. In time-response studies, we found that peripherally injected fluorescent-ghrelin quickly reaches hypothalamic regions located in apposition to the median eminence and more slowly reaches the periventricular hypothalamic parenchyma, adjacent to the dorsal part of the third ventricle. Additionally, we found that CSF ghrelin levels increase after the systemic administration of ghrelin, and that central infusions of either an anti-ghrelin antibody, which immuno-neutralizes CSF ghrelin, or a scrambled version of ghrelin, which is also internalized by cells of the blood-CSF barrier, partially impair the orexigenic effect of peripherally injected ghrelin. Thus, current evidence suggests that the blood-CSF barrier can transport circulating ghrelin into the brain, and that the access of ghrelin into the CSF is required for its full orexigenic effect.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/145491
url http://sedici.unlp.edu.ar/handle/10915/145491
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1559-1182
info:eu-repo/semantics/altIdentifier/issn/0893-7648
info:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-018-1362-8
info:eu-repo/semantics/altIdentifier/pmid/30276663
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
4120-4134
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