Aquaporin subtypes in rat cerebral microvessels

Kobayashi, Hideyuki; Minami, Shin-ichi; Itoh, Satoru; Shiraishi, Seiji; Yokoo, Hiroki; Yanagita, Toshihiko; Uezono, Yasuhito; Mohri, Motohiko; Wada, Akihiko

doi:10.1016/s0304-3940(00)01705-5

Cited by 57 publications

(40 citation statements)

References 18 publications

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“…They concluded that AQP4 is often "dissociated from the orthogonal arrays" and stated, "In our opinion, there is only one possible interpretation of these conflicting observations: in gliomatous membranes AQP4 must occur outside the OAPs." In possibly related observations, Kobayashi et al (2001) In this report, we provide additional ultrastructural and immunocytochemical characterizations confirming that AQP4 is the primary or sole intramembrane constituent of square arrays, both in astrocyte and ependymocytes of normal adult rat CNS, as well as in CHO cells transfected with two alternatively spliced variants of AQP4. In addition, we confirm that one variant of AQP4 (M1), when expressed alone and in abundance, does not form stable square arrays (Furman et al, 2003;Silberstein et al, 2004).…”

Section: Identification Of Aqp4 In "Square Arrays" Of Astrocytes and supporting

confidence: 68%

Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with models of AQP4 lattice assembly

et al. 2004

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Each day, approximately 0.5-0.9 l of water diffuses through (primarily) aquaporin-1 (AQP1) channels in the human choroid plexus, into the cerebrospinal fluid of the brain ventricles and spinal cord central canal, through the ependymal cell lining, and into the parenchyma of the CNS. Additional water is also derived from metabolism of glucose within the CNS parenchyma. To maintain osmotic homeostasis, an equivalent amount of water exits the CNS parenchyma by diffusion into interstitial capillaries and into the subarachnoid space that surrounds the brain and spinal cord. Most of that efflux is through AQP4 water channels concentrated in astrocyte endfeet that surround capillaries and form the glia limitans. This report extends the ultrastructural and immunocytochemical characterizations of the crystalline aggregates of intramembrane proteins that comprise the AQP4 "square arrays" of astrocyte and ependymocyte plasma membranes. We elaborate on recent demonstrations in Chinese hamster ovary cells of the effects on AQP4 array assembly resulting from separate vs. combined expression of M1 and M23 AQP4, which are two alternatively spliced variants of the AQP4 gene. Using improved shadowing methods, we demonstrate sub-molecular crossbridges that link the constituent intramembrane particles (IMPs) into regular square lattices of AQP4 arrays. We show that the AQP4 core particle is 4.5 nm in diameter, which appears to be too small to accommodate four monomeric proteins in a tetrameric IMP. Several structural models are considered that incorporate freeze-fracture data for submolecular "cross-bridges" linking IMPs into the classical square lattices that characterize, in particular, naturally occurring AQP4. Keywordscross-bridges; furrows; FRIL; plastic deformation; water homeostasis Precise control of water homeostasis is critical in the brain and spinal cord because even minor changes in water metabolism may result in brain edema and rapid development of potentially fatal compressive forces within the rigid encasement of the skull (King and Agre, 1996). Moderate hyponatremia may result in failure of synaptic transmission or in altered neuronal excitability (Kandel et al., 1992;Jefferys, 1995;Nielsen et al., 1997) and is a contributing factor in the pathogenesis of epilepsy (Dudek et al., 1990;Roper et al., 1992), whereas severe hyponatremia contributes to medical complications that arise from brain and spinal cord NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript trauma, brain tumors, neonatal hydrocephalus, acute water intoxication, and drowning (Johnson and Loewy, 1990;King and Agre, 1996;Nielsen et al., 1997).Rates of secretion vs. resorption of cerebrospinal fluid (CSF) is a major controlling factor in osmoregulation of the CNS. The aqueous component of CSF passes primarily through aquaporin-1 (AQP1) in the choroid plexus epithelium , with the remainder arising from metabolism of glucose, from simple transmembrane diffusion through cell membrane lipid bilayers [reviewed by Agre et al. (2...

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Section: Identification Of Aqp4 In "Square Arrays" Of Astrocytes and supporting

confidence: 68%

Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with models of AQP4 lattice assembly

et al. 2004

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“…Moreover, some studies have pointed to the possible presence of an endothelial pool of AQP4 in brain (8)(9)(10). This would be missing in constitutive knockout animals along with the endfoot pool, complicating the analysis of water transport at the blood-brain interface.…”

Section: Discussionmentioning

confidence: 99%

“…This conclusion was tempered by the controversy surrounding the exact distribution of AQP4 at the blood-brain interface. Notably, some data indicated that AQP4 was also present in endothelia (8)(9)(10)). An endothelial pool of AQP4, if any, would have been eliminated after global Aqp4 deletion and could have accounted for the reduced water absorption and edema formation in Aqp4 −/− animals.…”

mentioning

confidence: 99%

Glial-conditional deletion of aquaporin-4 ( Aqp4 ) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

Haj-Yasein

Vindedal

Eilert-Olsen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

291

264

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Tissue-and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement. edema | electron microscopy | homeostasis | membrane | swelling M ore than 100 y have elapsed since it was first shown that some solutes present in blood are retained by brain capillaries, pointing to the existence of a barrier function at the bloodbrain interface. This early finding naturally inspired a discussion as to what could constitute the morphological substrate of this barrier (1). With the advent of the electron microscope it became clear that the blood-brain interface is composed of endothelia and pericytes, surrounded by a basal lamina and perivascular endfeet of astrocytes. After decades of intense debate, a concept emerged that the functional barrier resides at the level of the endothelial cells (2). This was consistent with morphological data, which clearly showed that endothelia were continuous and coupled by tight junctions (3). The perivascular endfeet, on the other hand, were not coupled by tight junctions and were portrayed as a discontinuous layer with spacious clefts separating the individual processes.Discussions on the morphological substrate of barrier function have been focused on solutes (4), and the field has not yet matured to provide a consistent view regarding what cellular structures, if any, restrict water movement between blood and brain. Following the discovery of water channels, it became clear that the major brain water channel AQP4 is implicated in water transport at the blood-brain interface. Thus, global Aqp4 knockout significantly limited the development of brain edema, attesting to the importance of AQP4 water channels (4). As AQP4 is strongly expressed in the perivascular endfeet (5), the interest in these processes was rekindled also in the context of their possible barrier function.Specifically, it was proposed that the endfeet could restrict water flow, most significantly in pathophysiological se...

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“…We have found that AQP4 mRNA and protein were present in the microvessels prepared from rat cerebral cortex (6). In addition, the microvessels were immunochemically stained with anti-AQP4 antibody.…”

Section: Aqp4mentioning

confidence: 94%

Molecular Mechanisms and Drug Development in Aquaporin Water Channel Diseases: Aquaporins in the Brain

et al. 2004

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Abstract. Water homeostasis of the brain is essential for its neuronal activity. Changes in water content in the intra-and extra-cellular space affect ionic concentrations and therefore modify neuronal activity. Aquaporin (AQP) water channels may have a central role in keeping water homeostasis in the brain. Among AQP subtypes cloned in mammalian, only AQP1, AQP4, and AQP9 were identified in the brain. Changes in AQP expression may be correlated with edema formation of the brain. In this review, we describe the physiological function of AQPs and the regulatory mechanism of their expression in the brain.

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Aquaporin subtypes in rat cerebral microvessels

Cited by 57 publications

References 18 publications

Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with models of AQP4 lattice assembly

Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with models of AQP4 lattice assembly

Glial-conditional deletion of aquaporin-4 ( Aqp4 ) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

Molecular Mechanisms and Drug Development in Aquaporin Water Channel Diseases: Aquaporins in the Brain

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