Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Haj-Yasein NN,Vindedal GF,Eilert-Olsen M,Gundersen GA,Skare Ø,Laake P,Klungland A,Thorén AE,Burkhardt JM,Ottersen OP,Nagelhus EAdoi
10.1073/pnas.1110655108subject
Has Abstractpub_date
2011-10-25 00:00:00pages
17815-20issue
43eissn
0027-8424issn
1091-6490pii
1110655108journal_volume
108pub_type
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