Effect of C-type natriuretic peptide (CNP) on water channel aquaporin-4 (AQP4) expression in cultured astrocytes

The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells.

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Effects of agrin on the expression and distribution of the water channel protein aquaporin-4 and volume regulation in cultured astrocytes

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2007.05850.x ◽

2007 ◽

Vol 26 (8) ◽

pp. 2109-2118 ◽

Cited By ~ 57

Author(s):

Susan Noell ◽

Petra Fallier-Becker ◽

Cordian Beyer ◽

Stephan Kröger ◽

Andreas F. Mack ◽

...

Keyword(s):

Volume Regulation ◽

Water Channel ◽

Aquaporin 4 ◽

Channel Protein ◽

Cultured Astrocytes ◽

Water Channel Protein

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Immunohistochemical localization of aquaporin 4 (AQP4) in the porcine gastrointestinal tract

Acta Veterinaria Brno ◽

10.2754/avb201584040321 ◽

2015 ◽

Vol 84 (4) ◽

pp. 321-326 ◽

Cited By ~ 2

Author(s):

Marcin Bartłomiej Arciszewski ◽

Małgorzata Matysek ◽

Waldemar Sienkiewicz

Keyword(s):

Gastrointestinal Tract ◽

Epithelial Cells ◽

Colonic Mucosa ◽

Water Channel ◽

Immunohistochemical Localization ◽

Aquaporin 4 ◽

Enteric Neurons ◽

Aqp4 Expression ◽

Enteric Ganglia ◽

Strong Immunoreactivity

The water channel aquaporin-4 (AQP4) is a protein widely expressed on plasma membrane of a variety of epithelial cells. In this study we investigated the expression of AQP4 in the gastrointestinal tract of the pig using immunohistochemical staining. We found no presence of AQP4 in the different regions of the pig stomach. In the porcine small intestine moderate immunoreactivity to AQP4 was detected in enterocytes (along the villi and in the bottom of the crypts), duodenal Brunner’s glands and in enteric ganglia in cells lying in close vicinity to myenteric as well as submucous neurons. In superficial epithelial cells of the colonic mucosa as well as of caecal and colonic glands a very strong immunoreactivity to AQP4 was found. Both in the myenteric and submucous ganglia of the large intestine AQP4-positive cells surrounding enteric neurons were observed. We concluded that AQP4 expression in the porcine gastrointestinal tract showed some species-dependent differences in relation to other species. Based on the presented distribution pattern of AQP4, it is likely that the aquaporin plays a role in mucous (but not acid) secretion and intestinal absorptive processes in the pig.

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Protective Role of Early Aquaporin 4 Induction against Postischemic Edema Formation

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.133 ◽

2008 ◽

Vol 29 (2) ◽

pp. 423-433 ◽

Cited By ~ 98

Author(s):

Lorenz Hirt ◽

Béatrice Ternon ◽

Melanie Price ◽

Nabil Mastour ◽

Jean-François Brunet ◽

...

Keyword(s):

Water Channel ◽

Protective Role ◽

Aquaporin 4 ◽

Late Time ◽

Protective Mechanisms ◽

Edema Formation ◽

Aqp4 Expression ◽

Blood Brain Barrier Disruption ◽

Brain Barrier Disruption

Aquaporin 4 (AQP4) is a water channel involved in water movements across the cell membrane and is spatially organized on the cell surface in orthogonal array particles (OAPs). Its role in edema formation or resolution after stroke onset has been studied mainly at late time points. We have shown recently that its expression is rapidly induced after ischemia coinciding in time with an early swelling of the ischemic hemisphere. There are two isoforms of AQP4: AQP4-M1 and AQP4-M23. The ratio of these isoforms influences the size of the OAPs but the functional impact is not known. The role of the early induction of AQP4 is not yet known. Thrombin preconditioning in mice provides a useful model to study endogenous protective mechanisms. Using this model, we provide evidence for the first time that the early induction of AQP4 may contribute to limit the formation of edema and that the AQP4-M1 isoform is predominantly induced in the ischemic tissue at this time point. Although it prevents edema formation, the early induction of the AQP4 expression does not prevent the blood—brain barrier disruption, suggesting an effect limited to the prevention of edema formation possibly by removing of water from the tissue.

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Distribution of aquaporin-4 water channel expression within rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1995.269.6.f775 ◽

1995 ◽

Vol 269 (6) ◽

pp. F775-F785 ◽

Cited By ~ 65

Author(s):

J. Terris ◽

C. A. Ecelbarger ◽

D. Marples ◽

M. A. Knepper ◽

S. Nielsen

Keyword(s):

Collecting Duct ◽

Rat Kidney ◽

Basolateral Membrane ◽

Regional Distribution ◽

Water Channel ◽

Aquaporin 4 ◽

Molecular Water ◽

Water Restriction ◽

Aqp4 Expression ◽

Aquaporin 2

The aquaporins are a family of transmembrane proteins that function as molecular water channels. Recently, a mercurial-insensitive water channel [MIWC or aquaporin-4 (AQP4)] has been cloned, and its mRNA was found to be expressed strongly in kidney inner medulla and several nonrenal tissues. We prepared affinity-purified polyclonal antipeptide antibodies to AQP4 to define the regional distribution and cellular location of this water channel within the kidney. Immunoblotting of membrane fractions from different regions of the kidney revealed strongest expression in the base of the renal inner medulla, with detectable levels also in the inner medullary tip, but little or no expression in the outer medulla or cortex. Immunocytochemistry (light microscopy) revealed renal AQP4 labeling exclusively in the collecting duct principal cells, chiefly in the proximal two-thirds of the inner medullary collecting duct (IMCD). Little or no expression was seen in the outer medullary and cortical collecting ducts. Immunoelectron microscopy demonstrated AQP4 labeling of the basolateral membrane of IMCD cells, with relatively little labeling of intracellular vesicles. Differential centrifugation of inner medullary homogenates also revealed a lack of distribution to the vesicle-enriched fraction, which contains the vasopressin-regulated water channel, aquaporin-2. In contrast to aquaporin-2 and aquaporin-3, water restriction of rats did not increase the level of AQP4 expression. These results suggest a possible role for AQP4 in the basolateral exit of water from the IMCD.

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Aquaporin-4 dependent glymphatic solute transport in rodent brain

10.1101/216499 ◽

2017 ◽

Cited By ~ 4

Author(s):

Humberto Mestre ◽

Benjamin T. Kress ◽

Wenyan Zou ◽

Tinglin Pu ◽

Giridhar Murlidharan ◽

...

Keyword(s):

Solute Transport ◽

Healthy Aging ◽

Fluid Transport ◽

Water Channel ◽

Amyloid Β ◽

Aquaporin 4 ◽

Tau Proteins ◽

Glymphatic System ◽

Aqp4 Expression ◽

Transgenic Lines

AbstractThe glymphatic system is a brain-wide metabolite clearance pathway, impairment of which in post-traumatic and ischemic brain or healthy aging is proposed to contribute to intracerebral accumulation of amyloid-β and tau proteins. Glymphatic perivascular influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent publication that failed to find an effect of Aqp4 knockout on perivascular CSF tracer influx and interstitial fluid (ISF) tracer dispersion, four independent research groups have herein re-examined the importance of Aqp4 in glymphatic fluid transport. We concur in finding that CSF tracer influx, as well as fluorescently-tagged amyloid-β efflux, are significantly faster in wild-type mice than in three different transgenic lines featuring disruption of the Aqp4 gene and one line in which AQP4 expression lacks the critical perivascular localization (Snta1 knockout). These data validate the role of AQP4 in supporting fluid and solute transport and efflux in brain in accordance with the glymphatic system model.

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Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus

International Journal of Molecular Sciences ◽

10.3390/ijms22189745 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9745

Author(s):

José Luis Trillo-Contreras ◽

Juan José Toledo-Aral ◽

Javier Villadiego ◽

Miriam Echevarría

Keyword(s):

Cognitive Deficits ◽

Water Channel ◽

Aquaporin 4 ◽

Ependymal Cells ◽

Cerebral Tissue ◽

Principal Characteristics ◽

Aqp4 Expression ◽

Aged Mice ◽

The Brain ◽

Ventricular Distensibility

Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4−/− mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression.

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Aquaporin-4 protein expression in normal canine brains

BMC Veterinary Research ◽

10.1186/s12917-021-02745-9 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Patricia Álvarez ◽

Ester Blasco ◽

Martí Pumarola ◽

Annette Wessmann

Keyword(s):

White Matter ◽

Cancer Progression ◽

Aquaporin 4 ◽

Histopathological Study ◽

White Matter Tracts ◽

Aqp4 Expression ◽

Canine Brain ◽

Potential Marker ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded

Abstract Background Aquaporin-4 (AQP4) is in growing recognition as potential marker for cancer progression, differentiation and therapeutic intervention. No information is available about AQP4 expression in the normal canine brain. The aim of this histopathological study is to confirm the presence of AQP4 by immunohistochemistry technique in a group of non-pathological canine brains and to describe its expression and distribution across the brain. Results Twelve non-pathological canine brains of various ages (ranging from 21 days to 17 years) and breeds were included in the study. Immunohistochemical expression of AQP4 was analyzed using formalin-fixed paraffin-embedded brain tissue sections. The findings were correlated between AQP4 expressing cells and astrocytes using glial fibrillary acidic protein (GFAP). AQP4 expression was more marked in the astrocyte foot processes of subpial, perivascular and periventricular surfaces in all specimens. The majority of the canine brain sections (9/12) presented with an AQP4 predilection for white matter tracts. Interestingly, the two youngest dogs (21 days and 3 months old) were characterized by diffuse AQP4 labelling in both grey and white matter tracts. This result may suggest that brain development and ageing may play a role in the AQP4 distribution throughout the canine brain. Conclusions This is the first study to describe immunohistochemical distribution of AQP4 in normal canine brains. The AQP4 expression and distribution in non-pathological canine brains was comparable to other species. Larger studies are needed to substantiate the influence of breed and ageing on AQP4 expression in the normal canine brain.

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BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex

Scientific Reports ◽

10.1038/s41598-021-89997-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kazuya Morita ◽

Naoyuki Matsumoto ◽

Kengo Saito ◽

Toshihide Hamabe-Horiike ◽

Keishi Mizuguchi ◽

...

Keyword(s):

Cerebral Cortex ◽

Molecular Mechanisms ◽

Water Movement ◽

Water Channel ◽

Bmp Signaling ◽

Aquaporin 4 ◽

Mammalian Brain ◽

Physiological Conditions ◽

Pathological Conditions ◽

Mouse Cerebral Cortex

AbstractAquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood–brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.

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Aquaporin 4 over-expression in metastases to the brain in breast cancer.

10.31219/osf.io/yra9e ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Water Channel ◽

Breast Tumors ◽

Aquaporin 4 ◽

Primary Breast Tumor ◽

Over Expression ◽

Patients With Cancer ◽

Public Datasets ◽

The Brain

Brain metastases affect 10-15% of women with breast cancer (1). Metastasis is the most significant contributor to death in patients with cancer (2). We assessed what genes make brain metastases most different from the breast tumors from which they arose using public datasets (3, 4). The aquaporin 4 (AQP4) water channel (5) was one of the most differentially expressed genes in brain metastases when comparing the transcriptomes of matched tumor and metastasis samples from the brain and breast from 16 patients (2). Analysis of a separate dataset showed demonstrated the same result (4). In both cases, aquaporin 4 was expressed at significantly higher levels in metastases to the brain than in the primary breast tumor. This is the first report of aquaporin 4 differential over-expression in the brain metastases of patients with breast cancer.

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