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Cotransporter-mediated water transport underlying cerebrospinal fluid formation

Cerebrospinal fluid (CSF) production occurs at a rate of 500 ml per day in the adult human. Conventional osmotic forces do not suffice to support such production rate and the molecular mechanisms underlying this fluid production remain elusive. Using ex vivo choroid plexus live imaging and isotope f...

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Autores principales: Steffensen, Annette B., Oernbo, Eva K., Stoica, Anca, Gerkau, Niklas J., Barbuskaite, Dagne, Tritsaris, Katerina, Rose, Christine R., MacAulay, Nanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986890/
https://www.ncbi.nlm.nih.gov/pubmed/29867199
http://dx.doi.org/10.1038/s41467-018-04677-9
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author Steffensen, Annette B.
Oernbo, Eva K.
Stoica, Anca
Gerkau, Niklas J.
Barbuskaite, Dagne
Tritsaris, Katerina
Rose, Christine R.
MacAulay, Nanna
author_facet Steffensen, Annette B.
Oernbo, Eva K.
Stoica, Anca
Gerkau, Niklas J.
Barbuskaite, Dagne
Tritsaris, Katerina
Rose, Christine R.
MacAulay, Nanna
author_sort Steffensen, Annette B.
collection PubMed
description Cerebrospinal fluid (CSF) production occurs at a rate of 500 ml per day in the adult human. Conventional osmotic forces do not suffice to support such production rate and the molecular mechanisms underlying this fluid production remain elusive. Using ex vivo choroid plexus live imaging and isotope flux in combination with in vivo CSF production determination in mice, we identify a key component in the CSF production machinery. The Na(+)/K(+)/2Cl(−) cotransporter (NKCC1) expressed in the luminal membrane of choroid plexus contributes approximately half of the CSF production, via its unusual outward transport direction and its unique ability to directly couple water transport to ion translocation. We thereby establish the concept of cotransport of water as a missing link in the search for molecular pathways sustaining CSF production and redefine the current model of this pivotal physiological process. Our results provide a rational pharmacological target for pathologies involving disturbed brain fluid dynamics.
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spelling pubmed-59868902018-06-06 Cotransporter-mediated water transport underlying cerebrospinal fluid formation Steffensen, Annette B. Oernbo, Eva K. Stoica, Anca Gerkau, Niklas J. Barbuskaite, Dagne Tritsaris, Katerina Rose, Christine R. MacAulay, Nanna Nat Commun Article Cerebrospinal fluid (CSF) production occurs at a rate of 500 ml per day in the adult human. Conventional osmotic forces do not suffice to support such production rate and the molecular mechanisms underlying this fluid production remain elusive. Using ex vivo choroid plexus live imaging and isotope flux in combination with in vivo CSF production determination in mice, we identify a key component in the CSF production machinery. The Na(+)/K(+)/2Cl(−) cotransporter (NKCC1) expressed in the luminal membrane of choroid plexus contributes approximately half of the CSF production, via its unusual outward transport direction and its unique ability to directly couple water transport to ion translocation. We thereby establish the concept of cotransport of water as a missing link in the search for molecular pathways sustaining CSF production and redefine the current model of this pivotal physiological process. Our results provide a rational pharmacological target for pathologies involving disturbed brain fluid dynamics. Nature Publishing Group UK 2018-06-04 /pmc/articles/PMC5986890/ /pubmed/29867199 http://dx.doi.org/10.1038/s41467-018-04677-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Steffensen, Annette B.
Oernbo, Eva K.
Stoica, Anca
Gerkau, Niklas J.
Barbuskaite, Dagne
Tritsaris, Katerina
Rose, Christine R.
MacAulay, Nanna
Cotransporter-mediated water transport underlying cerebrospinal fluid formation
title Cotransporter-mediated water transport underlying cerebrospinal fluid formation
title_full Cotransporter-mediated water transport underlying cerebrospinal fluid formation
title_fullStr Cotransporter-mediated water transport underlying cerebrospinal fluid formation
title_full_unstemmed Cotransporter-mediated water transport underlying cerebrospinal fluid formation
title_short Cotransporter-mediated water transport underlying cerebrospinal fluid formation
title_sort cotransporter-mediated water transport underlying cerebrospinal fluid formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986890/
https://www.ncbi.nlm.nih.gov/pubmed/29867199
http://dx.doi.org/10.1038/s41467-018-04677-9
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