Removal of aquaporin-4 from glial and ependymal membranes causes brain water accumulation

Gry Fluge Vindedal; Anna E Thoren; Vidar Jensen; Arne Klungland; Yong Zhang; Michael J Holtzman; Ole Petter Ottersen; Erlend A Nagelhus

doi:10.1016/j.mcn.2016.10.004

Removal of aquaporin-4 from glial and ependymal membranes causes brain water accumulation

Mol Cell Neurosci. 2016 Dec:77:47-52. doi: 10.1016/j.mcn.2016.10.004. Epub 2016 Oct 14.

Authors

Gry Fluge Vindedal¹, Anna E Thoren², Vidar Jensen², Arne Klungland³, Yong Zhang⁴, Michael J Holtzman⁴, Ole Petter Ottersen⁵, Erlend A Nagelhus⁶

Affiliations

¹ 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.
² GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
³ 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.
⁴ Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
⁵ Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
⁶ 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.

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:Aqp4^flox/flox mice). 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.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Aquaporin 4 / genetics
Aquaporin 4 / metabolism*
Astrocytes / metabolism
Ependyma / cytology
Ependyma / metabolism*
Ependymoglial Cells / metabolism
Mice
Mice, Inbred C57BL
Water / metabolism

Substances

Aqp4 protein, mouse
Aquaporin 4
Water

Abstract

Publication types

MeSH terms

Substances

Grants and funding