Deletion of aquaporin-4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier
Article first published online: 30 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 60, Issue 3, pages 432–440, March 2012
How to Cite
Eilert-Olsen, M., Haj-Yasein, N. N., Vindedal, G. F., Enger, R., Gundersen, G. A., Hoddevik, E. H., Petersen, P. H., Haug, F.-M. S., Skare, Ø., Adams, M. E., Froehner, S. C., Burkhardt, J. M., Thoren, A. E. and Nagelhus, E. A. (2012), Deletion of aquaporin-4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier. Glia, 60: 432–440. doi: 10.1002/glia.22277
- Issue published online: 23 JAN 2012
- Article first published online: 30 NOV 2011
- Manuscript Accepted: 11 NOV 2011
- Manuscript Received: 18 NOV 2010
- US National Institutes of Health (NIH). Grant Number: NS33145
- Research Council of Norway (NevroNor, and FUGE grants), the Letten Foundation
- blood–brain barrier;
Expression of the water channel aquaporin-4 (AQP4) at the blood–brain interface is dependent upon the dystrophin associated protein complex. Here we investigated whether deletion of the Aqp4 gene affects the molecular composition of this protein scaffold and the integrity of the blood–brain barrier. High-resolution immunogold cytochemistry revealed that perivascular expression of α-syntrophin was reduced by 60% in Aqp4−/− mice. Additionally, perivascular AQP4 expression was reduced by 88% in α-syn−/− mice, in accordance with earlier reports. Immunofluorescence showed that Aqp4 deletion also caused a modest reduction in perivascular dystrophin, whereas β-dystroglycan labeling was unaltered. Perivascular microglia were devoid of AQP4 immunoreactivity. Deletion of Aqp4 did not alter the ultrastructure of capillary endothelial cells, the expression of tight junction proteins (claudin-5, occludin, and zonula occludens 1), or the vascular permeability to horseradish peroxidase and Evans blue albumin dye. We conclude that Aqp4 deletion reduces the expression of perivascular glial scaffolding proteins without affecting the endothelial barrier. Our data also indicate that AQP4 and α-syntrophin are mutually dependent upon each other for proper perivascular expression. © Wiley Periodicals, Inc.