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Choroid Plexus: Novel Functions for an Old Structure 2.0
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Choroid Plexus: Novel Functions for an Old Structure 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 10359

Special Issue Editors

Dr. Cecília R. Santos

E-Mail Website
Guest Editor
CICS-UBI—Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
Interests: neurodegeneration; choroid plexus
Special Issues, Collections and Topics in MDPI journals
Dr. Telma Quintela

E-Mail Website
Guest Editor
CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
Interests: circadian rhythm; blood-cerebrospinal fluid barrier; drug delivery; chronotherapy
Special Issues, Collections and Topics in MDPI journals
Dr. Isabel Goncalves

E-Mail Website
Guest Editor
CICS-UBI—Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
Interests: choroid plexus; brain barriers; chemical surveillance; taste and olfactory signaling; sex hormones
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Our first volume of the Special Issue "Choroid Plexus: Novel Functions for an Old Structure", clearly demonstrated the interest in the roles of the choroid plexus-cerebrospinal fluid system.

The first volume, highlighted the importance of the choroid plexus as a key player in the maintenance of the microenvironment of the central nervous system under both normal and pathological conditions.

We expect that the second volume of the Special Issue on "Choroid Plexus: Novel Functions for an Old Structure", continues to further increase and strengthen the knowledge of new choroid plexus functions in the pathophysiology of the central nervous system.

Dr. Cecília R. Santos
Dr. Telma Quintela
Dr. Isabel Goncalves
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Choroid plexus
  • Blood–cerebrospinal fluid barrier
  • Cerebrospinal fluid
  • Circadian clock

Published Papers (4 papers)

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Research

14 pages, 2027 KiB  
Article
The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate
by André Furtado, Rafael Mineiro, Ana Catarina Duarte, Isabel Gonçalves, Cecília R. Santos and Telma Quintela
Int. J. Mol. Sci. 2022, 23(5), 2443; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052443 - 23 Feb 2022
Cited by 4 | Viewed by 2037
Abstract
The choroid plexuses (CPs), located in the brain ventricles, form an interface between the blood and the cerebrospinal fluid named the blood-cerebrospinal barrier, which, by the presence of tight junctions, detoxification enzymes, and membrane transporters, limits the traffic of molecules into the central [...] Read more.
The choroid plexuses (CPs), located in the brain ventricles, form an interface between the blood and the cerebrospinal fluid named the blood-cerebrospinal barrier, which, by the presence of tight junctions, detoxification enzymes, and membrane transporters, limits the traffic of molecules into the central nervous system. It has already been shown that sex hormones regulate several CP functions, including the oscillations of its clock genes. However, it is less explored how the circadian rhythm regulates CP functions. This study aimed to evaluate the impact of sex hormones and circadian rhythms on the function of CP membrane transporters. The 24 h transcription profiles of the membrane transporters rAbca1, rAbcb1, rAbcc1, rAbcc4, rAbcg2, rAbcg4, and rOat3 were characterized in the CPs of intact male, intact female, sham-operated female, and gonadectomized rats. We found that rAbcc1 is expressed in a circadian way in the CPs of intact male rats, rAbcg2 in the CPs of intact female rats, and both rAbcc4 and rOat3 mRNA levels were expressed in a circadian way in the CPs of intact male and female rats. Next, using an in vitro model of the human blood–cerebrospinal fluid barrier, we also found that methotrexate (MTX) is transported in a circadian way across this barrier. The circadian pattern of Abcc4 found in the human CP epithelial papilloma cells might be partially responsible for MTX circadian transport across the basal membrane of CP epithelial cells. Full article
(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure 2.0)
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21 pages, 2186 KiB  
Article
OTX2 Homeoprotein Functions in Adult Choroid Plexus
by Anabelle Planques, Vanessa Oliveira Moreira, David Benacom, Clémence Bernard, Laurent Jourdren, Corinne Blugeon, Florent Dingli, Vanessa Masson, Damarys Loew, Alain Prochiantz and Ariel A. Di Nardo
Int. J. Mol. Sci. 2021, 22(16), 8951; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168951 - 19 Aug 2021
Cited by 5 | Viewed by 2744
Abstract
The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid [...] Read more.
The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative functional roles for OTX2 in adult choroid plexus function, including cell signaling and adhesion, and show that OTX2 regulates the expression of factors that are secreted into the cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and affects splicing, leading to changes in the mRNA isoforms of proteins that are implicated in the oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell-autonomous target regions, such as the visual cortex and subventricular zone, we identify putative targets that are involved in cell adhesion, chromatin structure, and RNA processing. Thus, OTX2 retains important roles for regulating choroid plexus function and brain homeostasis throughout life. Full article
(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure 2.0)
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17 pages, 2645 KiB  
Article
Effect of Lipopolysaccharide-Induced Inflammatory Challenge on β-Glucuronidase Activity and the Concentration of Quercetin and Its Metabolites in the Choroid Plexus, Blood Plasma and Cerebrospinal Fluid
by Małgorzata Domżalska, Wiesław Wiczkowski, Aleksandra Szczepkowska, Sylwia Chojnowska, Tomasz Misztal, Fruzsina R. Walter, Maria A. Deli, Hiroshi Ishikawa, Horst Schroten, Christian Schwerk and Janina Skipor
Int. J. Mol. Sci. 2021, 22(13), 7122; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137122 - 01 Jul 2021
Cited by 1 | Viewed by 2357
Abstract
Quercetin-3-glucuronide (Q3GA), the main phase II metabolite of quercetin (Q) in human plasma, is considered to be a more stable form of Q for transport with the bloodstream to tissues, where it can be potentially deconjugated by β-glucuronidase (β-Gluc) to Q aglycone, which [...] Read more.
Quercetin-3-glucuronide (Q3GA), the main phase II metabolite of quercetin (Q) in human plasma, is considered to be a more stable form of Q for transport with the bloodstream to tissues, where it can be potentially deconjugated by β-glucuronidase (β-Gluc) to Q aglycone, which easily enters the brain. This study evaluates the effect of lipopolysaccharide (LPS)-induced acute inflammation on β-Gluc gene expression in the choroid plexus (ChP) and its activity in blood plasma, ChP and cerebrospinal fluid (CSF), and the concentration of Q and its phase II metabolites in blood plasma and CSF. Studies were performed on saline- and LPS-treated adult ewes (n = 40) receiving Q3GA intravenously (n = 16) and on primary rat ChP epithelial cells and human ChP epithelial papilloma cells. We observed that acute inflammation stimulated β-Gluc activity in the ChP and blood plasma, but not in ChP epithelial cells and CSF, and did not affect Q and its phase II metabolite concentrations in plasma and CSF, except Q3GA, for which the plasma concentration was higher 30 min after administration (p < 0.05) in LPS- compared to saline-treated ewes. The lack of Q3GA deconjugation in the ChP observed under physiological and acute inflammatory conditions, however, does not exclude its possible role in the course of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure 2.0)
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27 pages, 25689 KiB  
Article
Multiple Na,K-ATPase Subunits Colocalize in the Brush Border of Mouse Choroid Plexus Epithelial Cells
by Inga Baasch Christensen, Lei Cheng, Jonathan R. Brewer, Udo Bartsch, Robert A. Fenton, Helle H. Damkier and Jeppe Praetorius
Int. J. Mol. Sci. 2021, 22(4), 1569; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041569 - 04 Feb 2021
Cited by 1 | Viewed by 2543
Abstract
(1) Background: The unusual accumulation of Na,K-ATPase complexes in the brush border membrane of choroid plexus epithelial cells have intrigued researchers for decades. However, the full range of the expressed Na,K-ATPase subunits and their relation to the microvillus cytoskeleton remains unknown. (2) Methods: [...] Read more.
(1) Background: The unusual accumulation of Na,K-ATPase complexes in the brush border membrane of choroid plexus epithelial cells have intrigued researchers for decades. However, the full range of the expressed Na,K-ATPase subunits and their relation to the microvillus cytoskeleton remains unknown. (2) Methods: RT-PCR analysis, co-immunoprecipitation, native PAGE, mass spectrometry, and differential centrifugation were combined with high-resolution immunofluorescence histochemistry, proximity ligase assays, and stimulated emission depletion (STED) microscopy on mouse choroid plexus cells or tissues in order to resolve these issues. (3) Results: The choroid plexus epithelium expresses Na,K-ATPase subunits α1, α2, β1, β2, β3, and phospholemman. The α1, α2, β1, and β2, subunits are all localized to the brush border membrane, where they appear to form a complex. The ATPase complexes may stabilize in the brush border membrane via anchoring to microvillar actin indirectly through ankyrin-3 or directly via other co-precipitated proteins. Aquaporin 1 (AQP1) may form part of the proposed multi-protein complexes in contrast to another membrane protein, the Na-K-2Cl cotransporter 1 (NKCC1). NKCC1 expression seems necessary for full brush border membrane accumulation of the Na,K-ATPase in the choroid plexus. (4) Conclusion: A multitude of Na,K-ATPase subunits form molecular complexes in the choroid plexus brush border, which may bind to the cytoskeleton by various alternative actin binding proteins. Full article
(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure 2.0)
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