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Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet.

Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement.

Pubmed ID: 21990350

Authors

  • Haj-Yasein NN
  • Vindedal GF
  • Eilert-Olsen M
  • Gundersen GA
  • Skare Ø
  • Laake P
  • Klungland A
  • Thorén AE
  • Burkhardt JM
  • Ottersen OP
  • Nagelhus EA

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 25, 2011

Associated Grants

None

Mesh Terms

  • Analysis of Variance
  • Animals
  • Aquaporin 4
  • Astrocytes
  • Blood-Brain Barrier
  • Blotting, Western
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Water