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Aquaporin-4 expression in the human choroid plexus

The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, t...

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Autores principales: Deffner, Felix, Gleiser, Corinna, Mattheus, Ulrich, Wagner, Andreas, Neckel, Peter H., Fallier-Becker, Petra, Hirt, Bernhard, Mack, Andreas F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785037/
https://www.ncbi.nlm.nih.gov/pubmed/35072772
http://dx.doi.org/10.1007/s00018-022-04136-1
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author Deffner, Felix
Gleiser, Corinna
Mattheus, Ulrich
Wagner, Andreas
Neckel, Peter H.
Fallier-Becker, Petra
Hirt, Bernhard
Mack, Andreas F.
author_facet Deffner, Felix
Gleiser, Corinna
Mattheus, Ulrich
Wagner, Andreas
Neckel, Peter H.
Fallier-Becker, Petra
Hirt, Bernhard
Mack, Andreas F.
author_sort Deffner, Felix
collection PubMed
description The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In this study, we analyzed the expression of aquaporins in the human CP using immunofluorescence and qPCR. As previously reported, AQP1 was expressed apically in CP epithelial cells. Surprisingly, and previously unknown, many cells in the CP epithelium were also positive for aquaporin-4 (AQP4), normally restricted to ventricle-lining ependymal cells and astrocytes in the brain. Expression of AQP1 and AQP4 was found in the CP of all eight body donors investigated (3 males, 5 females; age 74–91). These results were confirmed by qPCR, and by electron microscopy detecting orthogonal arrays of particles. To find out whether AQP4 expression correlated with the expression pattern of relevant transport-related proteins we also investigated expression of NKCC1, and Na/K-ATPase. Immunostaining with NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. We hypothesized that AQP4 expression in the CP was caused by age-related changes. To address this, we investigated mouse brains from young (2 months), adult (12 months) and old (30 months) mice. We found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Taken together, we provide evidence for AQP4 expression in the CP of the aging brain which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04136-1.
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spelling pubmed-87850372022-01-24 Aquaporin-4 expression in the human choroid plexus Deffner, Felix Gleiser, Corinna Mattheus, Ulrich Wagner, Andreas Neckel, Peter H. Fallier-Becker, Petra Hirt, Bernhard Mack, Andreas F. Cell Mol Life Sci Original Article The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In this study, we analyzed the expression of aquaporins in the human CP using immunofluorescence and qPCR. As previously reported, AQP1 was expressed apically in CP epithelial cells. Surprisingly, and previously unknown, many cells in the CP epithelium were also positive for aquaporin-4 (AQP4), normally restricted to ventricle-lining ependymal cells and astrocytes in the brain. Expression of AQP1 and AQP4 was found in the CP of all eight body donors investigated (3 males, 5 females; age 74–91). These results were confirmed by qPCR, and by electron microscopy detecting orthogonal arrays of particles. To find out whether AQP4 expression correlated with the expression pattern of relevant transport-related proteins we also investigated expression of NKCC1, and Na/K-ATPase. Immunostaining with NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. We hypothesized that AQP4 expression in the CP was caused by age-related changes. To address this, we investigated mouse brains from young (2 months), adult (12 months) and old (30 months) mice. We found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Taken together, we provide evidence for AQP4 expression in the CP of the aging brain which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04136-1. Springer International Publishing 2022-01-24 2022 /pmc/articles/PMC8785037/ /pubmed/35072772 http://dx.doi.org/10.1007/s00018-022-04136-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Deffner, Felix
Gleiser, Corinna
Mattheus, Ulrich
Wagner, Andreas
Neckel, Peter H.
Fallier-Becker, Petra
Hirt, Bernhard
Mack, Andreas F.
Aquaporin-4 expression in the human choroid plexus
title Aquaporin-4 expression in the human choroid plexus
title_full Aquaporin-4 expression in the human choroid plexus
title_fullStr Aquaporin-4 expression in the human choroid plexus
title_full_unstemmed Aquaporin-4 expression in the human choroid plexus
title_short Aquaporin-4 expression in the human choroid plexus
title_sort aquaporin-4 expression in the human choroid plexus
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785037/
https://www.ncbi.nlm.nih.gov/pubmed/35072772
http://dx.doi.org/10.1007/s00018-022-04136-1
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