scholarly journals Aquaporin-4 Expression in the Human Choroid Plexus

Author(s):  
Felix Deffner ◽  
Corinna Gleiser ◽  
Ulrich Mattheus ◽  
Andreas Wagner ◽  
Peter H Neckel ◽  
...  

Abstract 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.

2021 ◽  
Author(s):  
Felix Deffner ◽  
Corinna Gleiser ◽  
Ulrich Mattheus ◽  
Andreas Wagner ◽  
Peter H Neckel ◽  
...  

Abstract Background: The choroid plexus (CP) consists of specialized ependymal cells and underlying stroma and blood vessels, producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In contrast, ventricle-lining ependymal cells express aquaporin-4 (AQP4) basolaterallly. The initial purpose of this study was to analyze the expression of aquaporins in the ependyma – CP transition zone in the human brain to gain insights in aquaporin regulation. The results prompted us to investigate aquaporin expression in the mouse CP of different age groups. Methods: We analyzed the CP from eight body donors (age 74-91) applying immunofluorescence, qPCR, and freeze-fracture electron microscopy. We used antibodies against AQP1, AQP4, NKCC1, and Na/K-ATPase. In addition, we compared the CP from young (2 months), adult (12 months) and old (30 months) mice by qPCR and immunofluorescence. Results: Unexpectedly, many cells in the human CP were positive not only for AQP1 but also for AQP4, normally restricted to ependymal cells and astrocytes. Expression of AQP1 and AQP4 was found in the CP of all eight body donors. These results were confirmed by qPCR, and by electron microscopy detecting AQP4-specific orthogonal arrays of particles. To find out whether AQP4 expression correlated with relevant transport-related proteins we investigated expression of NKCC1 and Na/K-ATPase. Immunostaining for 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. To test for the possibility of age-related changes causing AQP4 expression in the CP, we analyzed mouse brains from different age groups and found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Conclusions: We provide evidence for AQP4 expression in the human and murine CP related to aging 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.


2019 ◽  
Vol 99 (8) ◽  
pp. 1245-1255 ◽  
Author(s):  
Alexa N. Lauer ◽  
Martin März ◽  
Svenja Meyer ◽  
Marita Meurer ◽  
Nicole de Buhr ◽  
...  

1977 ◽  
Vol 199 (1135) ◽  
pp. 321-326 ◽  

Choroid plexuses from early (30–60 days gestation) and late (125 days) sheep foetuses were examined by various ultrastructural techniques in order to investigate possible explanations for the greater penetration of protein and non-electrolytes from blood into cerebrospinal fluid (c. s. f.), which occurs in the early foetus in contrast to later stages. The greater penetration occurs despite the presence of well-formed tight junctions between the epithelial cells and the development of some of the characteristic ion gradients between c. s. f. and plasma. A tubulocisternal system of endoplasmic reticulum appears to connect the basolateral and the apical cell surfaces in the early but not in the late foetuses. Several types of connection between the endoplasmic reticulum and the cell membrane were present in the early foetuses; these may account for some of the different permeability properties of the immature choroid plexus.


Author(s):  
J. E. Michaels ◽  
P. A. Tornheim

In mammals, the caudal roof of the fourth ventricle consists of an inner layer of ependymal cells and an outer layer of leptomeningeal cells. It contains specializations in the form of tufts of choroid plexus for the elaboration of cerebrospinal fluid (CSF) as well as gross apertures that permit open communication between the ventricular system and the subarachnoid space, an essential feature for mammalian CSF circulation. In the bullfrog, as in most submammals, the roof of the fourth ventricle contains a rostral rhombencephalic choroid plexus with no gross evidence of fourth ventricular apertures. Communication between the ventricular system and the subarachnoid space in this animal, however, has been demonstrated to occur by way of microscopic openings or pores in the caudal roof of the hindbrain or the posterior rhombencephalic tela choroidea.


Author(s):  
Eelco F. M. Wijdicks ◽  
William D. Freeman

Cerebrospinal fluid (CSF) fills the subarachnoid space, spinal canal, and ventricles of the brain. CSF is enclosed within the brain by the pial layer, ependymal cells lining the ventricles, and the epithelial surface of the choroid plexus, where it is largely produced. Choroid plexus is present throughout the ventricular system with the exception of the frontal and occipital horns of the lateral ventricle and the cerebral aqueduct. The vascular smooth muscle and the epithelium of the choroid plexus receive both sympathetic and parasympathetic input. In an adult, CSF is normally acellular. A normal spinal sample may contain up to 5 white blood cells (WBCs) or red blood cells (RBCs). CSF allows for a route of delivery and removal of nutrients, hormones, and transmitters for the brain.


Neuroscience ◽  
2014 ◽  
Vol 260 ◽  
pp. 149-157 ◽  
Author(s):  
M. Ueno ◽  
N. Nishi ◽  
T. Nakagawa ◽  
Y. Chiba ◽  
I. Tsukamoto ◽  
...  

2017 ◽  
Vol 12 (1) ◽  
pp. 84 ◽  
Author(s):  
Yousef Sadeghi ◽  
Elham Hashemi ◽  
Abbas Aliaghaei ◽  
Afsoun Seddighi ◽  
Abbas Piryaei ◽  
...  

2007 ◽  
Vol 16 (7) ◽  
pp. 697-705 ◽  
Author(s):  
Dwaine F. Emerich ◽  
Patricia Schneider ◽  
Briannan Bintz ◽  
Jebecka Hudak ◽  
Christopher G. Thanos

Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3–4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells.


2013 ◽  
Vol 450 (1) ◽  
pp. 179-187 ◽  
Author(s):  
Hidekazu Fukuda ◽  
Taku Hirata ◽  
Nobuhiro Nakamura ◽  
Akira Kato ◽  
Katsumasa Kawahara ◽  
...  

Secretion of HCO3− at the apical side of the epithelial cells of the choroid plexus is an essential step in the formation of cerebrospinal fluid. Anion conductance with a high degree of HCO3− permeability has been observed and suggested to be the major pathway for HCO3− transport across the apical membrane. Recently, it was found that NBC (Na+/HCO3− co-transporter) 4, an electrogenic member of the NBC family, was expressed in the choroid plexus. We found that a novel variant of the NBC4 [NBC4g/Slc4a5 (solute carrier family 4, sodium bicarbonate co-transporter, member 5)] is almost exclusively expressed in the apical membrane of rat choroid plexus epithelium at exceptionally high levels. RNA interference-mediated knockdown allowed the functional demonstration that NBC4g is the major player in the HCO3− transport across the apical membrane of the choroid plexus epithelium. When combined with a recent observation that in choroid plexus epithelial cells electrogenic NBC operates with a stoichiometry of 3:1, the results of the present study suggest that NBC4g mediates the efflux of HCO3− and contributes to cerebrospinal fluid production.


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