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Choroid Plexus: Novel Functions for an Old Structure

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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 August 2020) | Viewed by 27146

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Special Issue Editors

Dr. Cecília R. Santos

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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

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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

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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,

Interest in the roles of the choroid plexus has noticeably increased in recent years.

The choroid plexus is a set of highly vascularized structures, located in the ventricular system of the brain that functions as a barrier at the interface between the blood and the cerebrospinal fluid.

The best-known functions of the choroid plexus are cerebrospinal fluid production and secretion, nutrient and hormone supply to the cerebrospinal fluid and brain, clearance of deleterious compounds and waste products, neuroimmune regulation, and stem cell proliferation and differentiation. Interestingly, emerging functions of the choroid plexus in the chemical surveillance of the central nervous system and as an extra-suprachiasmatic nucleus circadian clock highlight the possibility of sensing alterations in both the cerebrospinal and blood side, reacting to them in order to ensure brain homeostasis.

The implication of these new functions in the pathophysiology of the central nervous system deserves more attention.

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

Manuscript Submission Information

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Keywords

Choroid plexus
Blood–cerebrospinal fluid barrier
Cerebrospinal fluid
Circadian clock
Chemical surveillance
Taste and olfactory signaling
Brain disorders
Alzheimer´s disease

Published Papers (7 papers)

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Research

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16 pages, 2935 KiB

Open AccessArticle

Photoperiod Affects Leptin Action on the Choroid Plexus in Ewes Challenged with Lipopolysaccharide—Study on the mRNA Level

by Aleksandra Szczepkowska, Marta Kowalewska, Agata Krawczyńska, Andrzej P. Herman and Janina Skipor

Int. J. Mol. Sci. 2020, 21(20), 7647; https://doi.org/10.3390/ijms21207647 - 15 Oct 2020

Cited by 4 | Viewed by 2076

Abstract

The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (TLR4), proinflammatory cytokines (IL1B, IL6), their receptors (IL1R1, IL1R2, ILRN, IL6R, IL6ST) and inflammasome components necessary for pro-IL-1β activation (NLRP3, PYCARD, CASP1), chemokine (CCL2), leptin receptor isoforms (LEPRa, LEPRb) and a suppressor of cytokine signalling (SOCS3) in the ChP of ewes treated or not with lipopolysaccharide (LPS). Studies were conducted on adult female sheep divided into four groups (n = 6 in each): control, leptin (20 μg/kg), LPS (400 ng/kg), and LPS and leptin injected under SD and LD photoperiods. The leptin alone did not affect the gene expression but in co-treatment with LPS increased (p < 0.05) IL1B but only during SD, and SOCS3, IL1R2, IL1RN, IL6ST and CCL2 only during LD, and decreased (p < 0.05) the IL1R1 expression only during SD photoperiod. This indicates that the immunomodulatory action of leptin on the ChP is manifested only under the LPS challenge and is photoperiodically dependent. Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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12 pages, 1229 KiB

Open AccessArticle

Age, Sex Hormones, and Circadian Rhythm Regulate the Expression of Amyloid-Beta Scavengers at the Choroid Plexus

by Ana C. Duarte, André Furtado, Mariya V. Hrynchak, Ana R. Costa, Daniela Talhada, Isabel Gonçalves, Manuel C. Lemos, Telma Quintela and Cecília R.A. Santos

Int. J. Mol. Sci. 2020, 21(18), 6813; https://doi.org/10.3390/ijms21186813 - 17 Sep 2020

Cited by 16 | Viewed by 3915

Abstract

Accumulation of amyloid-beta (Aβ) in the brain is thought to derive from the impairment of Aβ clearance mechanisms rather than from its overproduction, which consequently contributes to the development of Alzheimer’s disease. The choroid plexus epithelial cells constitute an important clearance route for Aβ, either by facilitating its transport from the cerebrospinal fluid to the blood, or by synthesizing and secreting various proteins involved in Aβ degradation. Impaired choroid plexus synthesis, secretion, and transport of these Aβ-metabolizing enzymes have been therefore associated with the disruption of Aβ homeostasis and amyloid load. Factors such as aging, female gender, and circadian rhythm disturbances are related to the decline of choroid plexus functions that may be involved in the modulation of Aβ-clearance mechanisms. In this study, we investigated the impact of age, sex hormones, and circadian rhythm on the expression of Aβ scavengers such as apolipoprotein J, gelsolin, and transthyretin at the rat choroid plexus. Our results demonstrated that mRNA expression and both intracellular and secreted protein levels of the studied Aβ scavengers are age-, sex-, and circadian-dependent. These data suggest that the Aβ-degradation and clearance pathways at the choroid plexus, mediated by the presence of Aβ scavengers, might be compromised as a consequence of aging and circadian disturbances. These are important findings that enhance the understanding of Aβ-clearance-regulating mechanisms at the blood–cerebrospinal fluid barrier. Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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14 pages, 9963 KiB

Open AccessArticle

The Lactate Receptor HCA₁ Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle

by Alena Hadzic, Teresa D. Nguyen, Makoto Hosoyamada, Naoko H. Tomioka, Linda H. Bergersen, Jon Storm-Mathisen and Cecilie Morland

Int. J. Mol. Sci. 2020, 21(18), 6457; https://doi.org/10.3390/ijms21186457 - 04 Sep 2020

Cited by 10 | Viewed by 4400

Abstract

The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Nevertheless, few studies have focused on the main structure that produces CSF, the choroid plexus (CP). Due to the presence of monocarboxylate transporters (MCTs) in the CP, changes in blood and brain lactate levels are reflected in the CSF. A lactate receptor, the hydroxycarboxylic acid receptor 1 (HCA₁), is present in the brain, but whether it is located in the CP or in other periventricular structures has not been studied. Here, we investigated the distribution of HCA₁ in the cerebral ventricular system using monomeric red fluorescent protein (mRFP)-HCA₁ reporter mice. The reporter signal was only detected in the dorsal part of the third ventricle, where strong mRFP-HCA₁ labeling was present in cells of the CP, the tela choroidea, and the neuroepithelial ventricular lining. Co-labeling experiments identified these cells as fibroblasts (in the CP, the tela choroidea, and the ventricle lining) and ependymal cells (in the tela choroidea and the ventricle lining). Our data suggest that the HCA₁-containing fibroblasts and ependymal cells have the ability to respond to alterations in CSF lactate in body–brain signaling, but also as a sign of neuropathology (e.g., stroke and Alzheimer’s disease biomarker). Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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24 pages, 16439 KiB

Open AccessArticle

Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion

by Christian Wegele, Carolin Stump-Guthier, Selina Moroniak, Christel Weiss, Manfred Rohde, Hiroshi Ishikawa, Horst Schroten, Christian Schwerk, Michael Karremann and Julia Borkowski

Int. J. Mol. Sci. 2020, 21(16), 5739; https://doi.org/10.3390/ijms21165739 - 10 Aug 2020

Cited by 4 | Viewed by 3275

Abstract

Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood–brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood–cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis. Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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14 pages, 1114 KiB

Open AccessArticle

The Impact of Small Extracellular Vesicles on Lymphoblast Trafficking across the Blood-Cerebrospinal Fluid Barrier In Vitro

by Ulrike Erb, Julia Hikel, Svenja Meyer, Hiroshi Ishikawa, Thomas S. Worst, Katja Nitschke, Philipp Nuhn, Stefan Porubsky, Christel Weiss, Horst Schroten, Rüdiger Adam and Michael Karremann

Int. J. Mol. Sci. 2020, 21(15), 5491; https://doi.org/10.3390/ijms21155491 - 31 Jul 2020

Cited by 7 | Viewed by 2795

Abstract

Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on subsequent ALL transmigration across the barrier was studied in a human BCSFB in vitro model based on the HiBCPP cell line. The various cell lines markedly differed regarding exosome uptake to HiBCPP and biological significance. SD-1-derived exosomes associated to target cells unspecifically without detectable cellular effects. Whereas Nalm-6 and P12-derived exosomes incorporated by dynamin-dependent endocytosis, uptake in the latter could be diminished by integrin blocking. In addition, only P12-derived exosomes led to facilitated transmigration of the parental leukemia cells. In conclusion, we provide evidence that, to a varying extent, leukemia-derived exosomes may facilitate CNS invasion of ALL across the BCSFB without destruction of the barrier integrity. Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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Review

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24 pages, 2154 KiB

Open AccessReview

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

by Yoichi Chiba, Ryuta Murakami, Koichi Matsumoto, Keiji Wakamatsu, Wakako Nonaka, Naoya Uemura, Ken Yanase, Masaki Kamada and Masaki Ueno

Int. J. Mol. Sci. 2020, 21(19), 7230; https://doi.org/10.3390/ijms21197230 - 30 Sep 2020

Cited by 15 | Viewed by 4574

Abstract

The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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21 pages, 731 KiB

Open AccessReview

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

by Karol Kaiser and Vitezslav Bryja

Int. J. Mol. Sci. 2020, 21(13), 4760; https://doi.org/10.3390/ijms21134760 - 04 Jul 2020

Cited by 18 | Viewed by 5607

Abstract

Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions. Full article

(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)

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