Deletion of aquaporin-4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier

Glia. 2012 Mar;60(3):432-40. doi: 10.1002/glia.22277. Epub 2011 Nov 30.


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.

Publication types

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

MeSH terms

  • Animals
  • Aquaporin 4 / deficiency*
  • Aquaporin 4 / genetics
  • Blood Vessels / metabolism
  • Blood Vessels / ultrastructure
  • Blood-Brain Barrier / cytology*
  • Blood-Brain Barrier / metabolism*
  • Calcium-Binding Proteins / metabolism
  • Capillary Permeability / genetics
  • Cerebral Cortex / cytology
  • Endothelium / metabolism*
  • Endothelium / ultrastructure
  • Evans Blue
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / metabolism
  • Microscopy, Immunoelectron
  • Muscle Proteins / metabolism
  • Neuroglia / metabolism*
  • Neuroglia / ultrastructure
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism


  • Aif1 protein, mouse
  • Aquaporin 4
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Membrane Proteins
  • Microfilament Proteins
  • Muscle Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • syntrophin alpha1
  • Evans Blue