Deletion of aquaporin-4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier

Authors

  • Martine Eilert-Olsen,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Nadia Nabil Haj-Yasein,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Gry Fluge Vindedal,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
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  • Rune Enger,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Georg Andreas Gundersen,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Eystein Hellstrøm Hoddevik,

    1. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Pétur Henry Petersen,

    1. Department of Anatomy, Faculty of Medicine, Biomedical Center, University of Iceland, 101 Reykjavík, Iceland
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  • Finn-Mogens S. Haug,

    1. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Øivind Skare,

    1. Division of Epidemiology, Norwegian Institute of Public Health, 0403 Oslo, Norway
    2. Department of Public Health and Primary Health Care, University of Bergen, 5020 Bergen, Norway
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  • Marvin E. Adams,

    1. Department of Physiology and Biophysics, University of Washington, Seattle, Washington
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  • Stanley C. Froehner,

    1. Department of Physiology and Biophysics, University of Washington, Seattle, Washington
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  • John Michael Burkhardt,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
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  • Anna E. Thoren,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
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  • Erlend A. Nagelhus

    Corresponding author
    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway
    3. Department of Neurology, Oslo University Hospital, 0027 Oslo, Norway
    • MD, PhD, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318 Oslo, Norway
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Abstract

Expression of the water channel aquaporin-4 (AQP4) at the blood–brain interface is dependent upon the dystrophin associated protein complex. Here we investigated whether deletion of the Aqp4 gene affects the molecular composition of this protein scaffold and the integrity of the blood–brain barrier. High-resolution immunogold cytochemistry revealed that perivascular expression of α-syntrophin was reduced by 60% in Aqp4−/− mice. Additionally, perivascular AQP4 expression was reduced by 88% in α-syn−/− mice, in accordance with earlier reports. Immunofluorescence showed that Aqp4 deletion also caused a modest reduction in perivascular dystrophin, whereas β-dystroglycan labeling was unaltered. Perivascular microglia were devoid of AQP4 immunoreactivity. Deletion of Aqp4 did not alter the ultrastructure of capillary endothelial cells, the expression of tight junction proteins (claudin-5, occludin, and zonula occludens 1), or the vascular permeability to horseradish peroxidase and Evans blue albumin dye. We conclude that Aqp4 deletion reduces the expression of perivascular glial scaffolding proteins without affecting the endothelial barrier. Our data also indicate that AQP4 and α-syntrophin are mutually dependent upon each other for proper perivascular expression. © Wiley Periodicals, Inc.

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