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      Immunohistochemical localization and mRNA expression of aquaporins in the macula utriculi of patients with Meniere’s disease and acoustic neuroma

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          Abstract

          Meniere’s disease is nearly invariably associated with endolymphatic hydrops (the net accumulation of water in the inner ear endolymphatic space). Vestibular maculae utriculi were acquired from patients undergoing surgery for Meniere’s disease and acoustic neuroma and from autopsy (subjects with normal hearing and balance). Quantitative immunostaining was conducted with antibodies against aquaporins (AQPs) 1, 4, and 6, Na +K +ATPase, Na +K +2Cl co-transporter (NKCC1), and α-syntrophin. mRNA was extracted from the surgically acquired utricles from subjects with Meniere’s disease and acoustic neuroma to conduct quantitative real-time reverse transcription with polymerase chain reaction for AQP1, AQP4, and AQP6. AQP1 immunoreactivity (−IR) was located in blood vessels and fibrocytes in the underlying stroma, without any apparent alteration in Meniere’s specimens when compared with acoustic neuroma and autopsy specimens. AQP4-IR localized to the epithelial basolateral supporting cells in Meniere’s disease, acoustic neuroma, and autopsy. In specimens from subjects with Meniere’s disease, AQP4-IR was significantly decreased compared with autopsy and acoustic neuroma specimens. AQP6-IR occurred in the sub-apical vestibular supporting cells in acoustic neuroma and autopsy samples. However, in Meniere’s disease specimens, AQP6-IR was significantly increased and diffusely redistributed throughout the supporting cell cytoplasm. Na +K +ATPase, NKCC1, and α-syntrophin were expressed within sensory epithelia and were unaltered in Meniere’s disease specimens. Expression of AQP1, AQP4, or AQP6 mRNA did not differ in vestibular endorgans from patients with Meniere’s disease. Changes in AQP4 (decreased) and AQP6 (increased) expression in Meniere’s disease specimens suggest that the supporting cell might be a cellular target.

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          Most cited references54

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          Aquaporin water channels--from atomic structure to clinical medicine.

          The water permeability of biological membranes has been a longstanding problem in physiology, but the proteins responsible for this remained unknown until discovery of the aquaporin 1 (AQP1) water channel protein. AQP1 is selectively permeated by water driven by osmotic gradients. The atomic structure of human AQP1 has recently been defined. Each subunit of the tetramer contains an individual aqueous pore that permits single-file passage of water molecules but interrupts the hydrogen bonding needed for passage of protons. At least 10 mammalian aquaporins have been identified, and these are selectively permeated by water (aquaporins) or water plus glycerol (aquaglyceroporins). The sites of expression coincide closely with the clinical phenotypes--ranging from congenital cataracts to nephrogenic diabetes insipidus. More than 200 members of the aquaporin family have been found in plants, microbials, invertebrates and vertebrates, and their importance to the physiology of these organisms is being uncovered.
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            Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Menière's disease. American Academy of Otolaryngology-Head and Neck Foundation, Inc.

            EM Monsell (1995)
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              The molecular basis of water transport in the brain.

              Brain function is inextricably coupled to water homeostasis. The fact that most of the volume between neurons is occupied by glial cells, leaving only a narrow extracellular space, represents an important challenge, as even small extracellular volume changes will affect ion concentrations and therefore neuronal excitability. Further, the ionic transmembrane shifts that are required to maintain ion homeostasis during neuronal activity must be accompanied by water. It follows that the mechanisms for water transport across plasma membranes must have a central part in brain physiology. These mechanisms are also likely to be of pathophysiological importance in brain oedema, which represents a net accumulation of water in brain tissue. Recent studies have shed light on the molecular basis for brain water transport and have identified a class of specialized water channels in the brain that might be crucial to the physiological and pathophysiological handling of water.
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                Author and article information

                Contributors
                +1-310-8255331 , ishiyama@ucla.edu
                Journal
                Cell Tissue Res
                Cell and Tissue Research
                Springer-Verlag (Berlin/Heidelberg )
                0302-766X
                1432-0878
                12 May 2010
                12 May 2010
                June 2010
                : 340
                : 3
                : 407-419
                Affiliations
                [1 ]Neurology Department, Division of Head and Neck “David Geffen” School of Medicine, UCLA, Los Angeles, CA USA
                [2 ]Surgery Department, Division of Head and Neck “David Geffen” School of Medicine, UCLA, Los Angeles, CA USA
                [3 ]CHS 62-132, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095 USA
                Article
                975
                10.1007/s00441-010-0975-7
                2882038
                20461409
                a2018603-213c-42c6-b548-9b064515ffa6
                © The Author(s) 2010
                History
                : 29 December 2009
                : 31 March 2010
                Categories
                Regular Article
                Custom metadata
                © Springer-Verlag 2010

                Molecular medicine
                inner ear,endolymphatic hydrops,acoustic neuroma,na+k+atpase,nkcc1,α-syntrophin,aquaporins,human

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