scholarly journals Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
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.

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

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150945 ◽  
Author(s):  
Nathalie Strazielle ◽  
Rita Creidy ◽  
Christophe Malcus ◽  
José Boucraut ◽  
Jean-François Ghersi-Egea
Keyword(s):  
T Lymphocytes ◽  
Choroid Plexus ◽  
Choroid Plexus Epithelium ◽  
The Brain

scholarly journals Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

2016 ◽  
Vol 41 (5) ◽  
pp. E10 ◽  
Author(s):  
Jason K. Karimy ◽  
Daniel Duran ◽  
Jamie K. Hu ◽  
Charuta Gavankar ◽  
Jonathan R. Gaillard ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Past Century ◽  
Choroid Plexus Epithelium ◽  
Hydrodynamic Models ◽  
Molecular Physiology ◽  
Pediatric Hydrocephalus ◽  
Shunt Dependence

Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

scholarly journals Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1257
Author(s):  
Maria Assunta Potenza ◽  
Luca Sgarra ◽  
Vanessa Desantis ◽  
Carmela Nacci ◽  
Monica Montagnani
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Senile Plaques ◽  
Mitochondrial Activity ◽  
Enhanced Production ◽  
The Common ◽  
The Brain

A growing number of clinical and epidemiological studies support the hypothesis of a tight correlation between type 2 diabetes mellitus (T2DM) and the development risk of Alzheimer’s disease (AD). Indeed, the proposed definition of Alzheimer’s disease as type 3 diabetes (T3D) underlines the key role played by deranged insulin signaling to accumulation of aggregated amyloid beta (Aβ) peptides in the senile plaques of the brain. Metabolic disturbances such as hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and chronic inflammation associated with T2DM are responsible for an inefficient transport of insulin to the brain, producing a neuronal insulin resistance that triggers an enhanced production and deposition of Aβ and concomitantly contributes to impairment in the micro-tubule-associated protein Tau, leading to neural degeneration and cognitive decline. Furthermore, the reduced antioxidant capacity observed in T2DM patients, together with the impairment of cerebral glucose metabolism and the decreased performance of mitochondrial activity, suggests the existence of a relationship between oxidative damage, mitochondrial impairment, and cognitive dysfunction that could further reinforce the common pathophysiology of T2DM and AD. In this review, we discuss the molecular mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the pathogenesis and progression of AD, deepening the analysis of complex mechanisms involved in reactive oxygen species (ROS) production under oxidative stress and their possible influence in AD and T2DM. In addition, the role of current therapies as tools for prevention or treatment of damage induced by oxidative stress in T2DM and AD will be debated.

scholarly journals Epithelial Pathways in Choroid Plexus Electrolyte Transport

Physiology ◽  
2010 ◽  
Vol 25 (4) ◽  
pp. 239-249 ◽  
Author(s):  
Helle H. Damkier ◽  
Peter D. Brown ◽  
Jeppe Praetorius
Keyword(s):  
Cerebrospinal Fluid ◽  
Chemical Composition ◽  
Choroid Plexus ◽  
Interstitial Fluid ◽  
Electrolyte Transport ◽  
Molecular Pathways ◽  
Choroid Plexus Epithelium ◽  
Neuronal Function ◽  
The Brain

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.

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

2004 ◽  
Vol 286 (3) ◽  
pp. C601-C610 ◽  
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.

scholarly journals Localization of metallothionein in the brain of rat and mouse.

1992 ◽  
Vol 40 (2) ◽  
pp. 309-315 ◽  
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.

scholarly journals Transport across the choroid plexus epithelium

2017 ◽  
Vol 312 (6) ◽  
pp. C673-C686 ◽  
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.

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

1997 ◽  
Vol 94 (1) ◽  
pp. 283-286 ◽  
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

Organization of tight junctions in the choroid plexus epithelium

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.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

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