T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium

A stable intraventricular milieu is crucial for maintaining normal neuronal function. The choroid plexus epithelium produces the cerebrospinal fluid and in doing so influences the chemical composition of the interstitial fluid of the brain. Here, we review the molecular pathways involved in transport of the electrolytes Na+, K+, Cl−, and HCO3− across the choroid plexus epithelium.

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A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.00240.2003 ◽

2004 ◽

Vol 286 (3) ◽

pp. C601-C610 ◽

Cited By ~ 67

Author(s):

J. Praetorius ◽

L. N. Nejsum ◽

S. Nielsen

Keyword(s):

Cerebrospinal Fluid ◽

Plasma Membrane ◽

Choroid Plexus ◽

Gene Product ◽

Pcr Analysis ◽

Membrane Domain ◽

Choroid Plexus Epithelium ◽

Basolateral Plasma Membrane ◽

Plasma Membrane Domain ◽

The Brain

The choroid plexus epithelium of the brain ventricular system produces the majority of the cerebrospinal fluid and thereby defines the ionic composition of the interstitial fluid in the brain. The transepithelial movement of Na+ and water in the choroid plexus depend on a yet-unidentified basolateral stilbene-sensitive [Formula: see text]-[Formula: see text] uptake protein. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression in the choroid plexus of SLC4A10 mRNA, which encodes a stilbene-sensitive [Formula: see text]-[Formula: see text] transporter. Anti-COOH-terminal antibodies were developed to determine the specific expression and localization of this [Formula: see text]-[Formula: see text] transport protein. Immunoblotting demonstrated antibody binding to a 180-kDa protein band from mouse and rat brain preparations enriched with choroid plexus. The immunoreactive band migrated as a 140-kDa protein after N-deglycosylation, consistent with the predicted molecular size of the SLC4A10 gene product. Bright-field immunohistochemistry and immunoelectron microscopy demonstrated strong labeling confined to the basolateral plasma membrane domain of the choroid plexus epithelium. Furthermore, the stilbene-insensitive [Formula: see text]-[Formula: see text] cotransporter, NBCn1, was also localized to the basolateral plasma membrane domain of the choroid plexus epithelium. Hence, we propose that the SLC4A10 gene product and NBCn1 both function as basolateral [Formula: see text] entry pathways and that the SLC4A10 gene product may be responsible for the stilbene-sensitive [Formula: see text]-[Formula: see text] uptake that is essential for cerebrospinal fluid production.

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Localization of metallothionein in the brain of rat and mouse.

Journal of Histochemistry & Cytochemistry ◽

10.1177/40.2.1552172 ◽

1992 ◽

Vol 40 (2) ◽

pp. 309-315 ◽

Cited By ~ 77

Author(s):

N Nishimura ◽

H Nishimura ◽

A Ghaffar ◽

C Tohyama

Keyword(s):

Endothelial Cells ◽

Choroid Plexus ◽

Glial Cells ◽

Adult Mouse ◽

Ependymal Cells ◽

Choroid Plexus Epithelium ◽

Pia Mater ◽

Adult Mouse Brain ◽

Adult Rats ◽

The Brain

Metallothionein (MT) is a low molecular mass protein inducible by heavy metals such as cadmium (Cd), zinc, and copper, and having high affinity for these metals. In the present study, we investigated the immunohistological localization of MT in the brains of rats and mice. In adult rat brain, almost no MT immunostaining was observed, whereas in adult mouse brain strong MT immunostaining was found in the ependymal cells, some glial cells, arachnoid, and pia mater. No immunostaining was detected in neurons and endothelial cells. In younger rats (1-3 weeks old), strong MT immunostaining was observed in ependymal cells, choroid plexus epithelium, arachnoid, and pia mater. The overall MT concentration in adult mouse brain appeared higher than that of the brains of young and adult rats. When adult rats were administered Cd, MT was induced not only in some glial cells, ependymal cells, arachnoid, and pia mater but also in endothelial cells. Although Cd treatment resulted in an increase in the MT immunostaining in the specific cells described above, the MT induction was not great enough to significantly affect the overall MT level in the brain. The present result suggest a possible link of MT with cell growth of choroid plexus epithelium and ependymal cells, as well as a detoxifying role of MT in the blood-brain barrier and the cerebrospinal fluid-brain barrier.

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Transport across the choroid plexus epithelium

AJP Cell Physiology ◽

10.1152/ajpcell.00041.2017 ◽

2017 ◽

Vol 312 (6) ◽

pp. C673-C686 ◽

Cited By ~ 39

Author(s):

Jeppe Praetorius ◽

Helle Hasager Damkier

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Choroid Plexus ◽

System Development ◽

Nervous System Development ◽

Ionic Balance ◽

Choroid Plexus Epithelium ◽

The Central Nervous System ◽

The Brain

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy.

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The choroid plexus epithelium is the site of the organic anion transport protein in the brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.94.1.283 ◽

1997 ◽

Vol 94 (1) ◽

pp. 283-286 ◽

Cited By ~ 94

Author(s):

R. H. Angeletti ◽

P. M. Novikoff ◽

S. R. Juvvadi ◽

J.-M. Fritschy ◽

P. J. Meier ◽

...

Keyword(s):

Choroid Plexus ◽

Organic Anion ◽

Anion Transport ◽

Transport Protein ◽

Organic Anion Transport ◽

Choroid Plexus Epithelium ◽

The Brain

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Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/805405 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 14

Author(s):

Teo Vargas ◽

Desiree Antequera ◽

Cristina Ugalde ◽

Carlos Spuch ◽

Eva Carro

Keyword(s):

Choroid Plexus ◽

Molecular Mechanisms ◽

Prophylactic Treatment ◽

Senile Plaques ◽

Choroid Plexus Epithelium ◽

Amyloid Deposits ◽

Cytoskeletal Disruption ◽

The Brain ◽

Epithelial Cell Death ◽

Cerebrovascular Amyloid

Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-β(Aβ) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying Aβaccumulation at the choroid plexus epithelium remain unclear. Aβclearance, from the brain to the blood, involves Aβcarrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces Aβ-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing Aβ-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD.

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Organization of tight junctions in the choroid plexus epithelium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082546 ◽

1978 ◽

Vol 36 (2) ◽

pp. 336-337

Author(s):

B. Van Deurs ◽

J. K. Koehler

Keyword(s):

Choroid Plexus ◽

Present Report ◽

Freeze Fracture ◽

Barrier Properties ◽

Cell Junctions ◽

Structural Basis ◽

Apical Surface ◽

Choroid Plexus Epithelium ◽

Solid Nitrogen ◽

Special Composition

The choroid plexus epithelium constitutes a blood-cerebrospinal fluid (CSF) barrier, and is involved in regulation of the special composition of the CSF. The epithelium is provided with an ouabain-sensitive Na/K-pump located at the apical surface, actively pumping ions into the CSF. The choroid plexus epithelium has been described as “leaky” with a low transepithelial resistance, and a passive transepithelial flux following a paracellular route (intercellular spaces and cell junctions) also takes place. The present report describes the structural basis for these “barrier” properties of the choroid plexus epithelium as revealed by freeze fracture.Choroid plexus from the lateral, third and fourth ventricles of rats were used. The tissue was fixed in glutaraldehyde and stored in 30% glycerol. Freezing was performed either in liquid nitrogen-cooled Freon 22, or directly in a mixture of liquid and solid nitrogen prepared in a special vacuum chamber. The latter method was always used, and considered necessary, when preparations of complementary (double) replicas were made.

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Neuroinflammation and protein pathology in Parkinson’s disease dementia

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01083-5 ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Antonina Kouli ◽

Marta Camacho ◽

Kieren Allinson ◽

Caroline H. Williams-Gray

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

T Lymphocytes ◽

Substantia Nigra ◽

Amyloid Β ◽

Brain Regions ◽

Parkinson’S Disease Dementia ◽

Activated Microglia ◽

Cell Counts ◽

The Brain

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

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Thiamine transport in the central nervous system

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.4.1101 ◽

1976 ◽

Vol 230 (4) ◽

pp. 1101-1107 ◽

Cited By ~ 39

Author(s):

R Spector

Keyword(s):

Choroid Plexus ◽

Intraventricular Injection ◽

Simple Diffusion ◽

Thiamine Transport ◽

Choroid Plexuses ◽

The Central Nervous System ◽

The Brain ◽

Thiamine Phosphates

Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

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Analysis of Changes in Signal Intensity of Choroid Plexus in MRI Using FLAIR-DW-EPI Pulse Sequence

ScholarGen Publishers ◽

10.31916/sjmi2020-01-02 ◽

2020 ◽

Vol 3 (1) ◽

pp. 9-15

Author(s):

Jingyu Kim ◽

◽

Sang-Jin Im ◽

Keyword(s):

Choroid Plexus ◽

Signal Intensity ◽

Pulse Sequence ◽

Signal Strength ◽

Brain Parenchyma ◽

Weighted Image ◽

Diffusion Weighted ◽

Water Signal ◽

The Brain ◽

Functional Problems

In this study, the signal intensity of choroid plexus, which is producing cerebrospinal fluid, is analyzed according to the FLAIR diffusion-weighted imaging technique. In the T2*-DW-EPI diffusion-weighted image, the FLAIR-DW-EPI technique, which suppressed the water signal, was additionally examined for subjects with high choroid plexus signals and compared and analyzed the signal intensity. As a result of the experiment, it was confirmed that the FLAIR-DW-EPI technique showed a signal strength equal to or lower than that of the brain parenchyma, and there was a difference in signal strength between the two techniques. As a result of this study, if the choroidal plexus signal is high in the T2 * -DW-EPI diffusionweighted image, additional examination of the FLAIR-DW-EPI technique is thought to be useful in distinguishing functional problems of the choroid plexus. In conclusion, if the choroidal plexus signal is high on the T2*-DW-EPI diffuse weighted image, it is thought that further examination of the FLAIR-DW-EPI technique will be useful in distinguishing functional problems of the choroidal plexus.

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