title: Removal of aquaporin-4 from glial and ependymal membranes causes brain water accumulation.
abstract: There is a constitutive production of water in brain. The efflux routes of this excess water remain to be identified. We used basal brain water content as a proxy for the capacity of water exit routes. Basal brain water content was increased in mice with a complete loss of aquaporin-4 (AQP4) water channels (global Aqp4-/-mice), but not in mice with a selective removal of perivascular AQP4 or in a novel mouse line with a selective deletion of ependymal AQP4 (Foxj1-Cre:Aqp4flox/floxmice). Unique for the global Aqp4-/-mice is the loss of the AQP4 pool subjacent to the pial membrane. Our data suggest that water accumulates in brain when subpial AQP4 is missing, pointing to a critical role of this pool of water channels in brain water exit.
authors.affiliation: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway; GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Gry Fluge
authors.initials: GF
authors.lastname: Vindedal
authors.affiliation: GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Thoren
authors.affiliation: GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Vidar
authors.initials: V
authors.lastname: Jensen
authors.affiliation: Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
authors.affiliation: Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Ottersen
authors.affiliation: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway; GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway; Department of Neurology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway. Electronic address: e.a.nagelhus@medisin.uio.no.
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D004805:Ependyma / Q000166:cytology / Q000378:metabolism*; D063928:Ependymoglial Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014867:Water / Q000378:metabolism
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D014867:Water
keywords: AQP4; Alpha-syntrophin; Aquaporin; Astrocytes; Brain edema; CSF; Cerebrospinal fluid; Endfeet; Ependyma; Extracellular space; Foxj1; Glia; Glymphatic; Interstitial fluid; Neuron-glial; Paravascular; Water homeostasis