Aquaporin-4 regulates extracellular space volume dynamics during high-frequency synaptic stimulation: A gene deletion study in mouse hippocampus

Authors

  • Nadia Nabil Haj-Yasein,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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    • The first two authors contributed equally to this work.

  • Vidar Jensen,

    1. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
    2. Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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    • The first two authors contributed equally to this work.

  • Ivar Østby,

    1. Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway
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  • Stig W. Omholt,

    1. Centre for Integrative Genetics (CIGENE), Norwegian University of Life Sciences, Ås, Norway
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  • Juha Voipio,

    1. Department of Biosciences, University of Helsinki, Helsinki, Finland
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  • Kai Kaila,

    1. Department of Biosciences, University of Helsinki, Helsinki, Finland
    2. Neuroscience Center, University of Helsinki, Helsinki, Finland
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  • Ole P. Ottersen,

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

    1. Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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  • Erlend A. Nagelhus

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

Little is known about the physiological roles of aquaporin-4 (AQP4) in the central nervous system. AQP4 water channels are concentrated in endfeet membranes of astrocytes but also localize to the fine astrocytic processes that abut central synapses. Based on its pattern of expression, we predicted that AQP4 could be involved in controlling water fluxes and changes in extracellular space (ECS) volume that are associated with activation of excitatory pathways. Here, we show that deletion of Aqp4 accentuated the shrinkage of the ECS that occurred in the mouse hippocampal CA1 region during activation of Schaffer collateral/commissural fibers. This effect was found in the stratum radiatum (where perisynaptic astrocytic processes abound) but not in the pyramidal cell layer (where astrocytic processes constitute but a minor volume fraction). For both genotypes the ECS shrinkage was most pronounced in the pyramidal cell layer. Our data attribute a physiological role to AQP4 and indicate that this water channel regulates extracellular volume dynamics in the mammalian brain. © 2012 Wiley Periodicals, Inc.

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