Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling.

Abstract

Aquaporin-4 (AQP4) is a water transport protein expressed in glial cell plasma membranes, including glial cell foot processes lining the blood-brain barrier. AQP4 deletion in mice reduces cytotoxic brain edema produced by different pathologies. To determine whether AQP4 is rate-limiting for brain water accumulation and whether altered AQP4 expression, as occurs in various pathologies, could have functional importance, we generated mice that overexpressed AQP4 in brain glial cells by a transgenic approach using the glial fibrillary acid protein promoter. Overexpression of AQP4 protein in brain by approximately 2.3-fold did not affect mouse survival, appearance, or behavior, nor did it affect brain anatomy or intracranial pressure (ICP). However, following acute water intoxication produced by intraperitoneal water injection, AQP4-overexpressing mice had an accelerated progression of cytotoxic brain swelling, with ICP elevation of 20 +/- 2 mmHg at 10 min, often producing brain herniation and death. In contrast, ICP elevation was 14 +/- 2 mmHg at 10 min in control mice and 9.8 +/- 2 mmHg in AQP4 knock-out mice. The deduced increase in brain water content correlated linearly with brain AQP4 protein expression. We conclude that AQP4 expression is rate-limiting for brain water accumulation, and thus, that altered AQP4 expression can be functionally significant.

• Authors: Baoxue Yang, Zsolt Zador, A S Verkman
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 283 Issue 22 Pg. 15280-6 (May 30 2008) ISSN: 0021-9258 [Print] United States
• PMID: 18375385 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Aqp4 protein, mouse
• Aquaporin 4
• Glial Fibrillary Acidic Protein

Topics

• Animals
• Aquaporin 4 (biosynthesis, genetics)
• Biological Transport (genetics)
• Blood-Brain Barrier (metabolism, pathology)
• Brain Edema (genetics, metabolism, pathology)
• Cell Membrane (genetics, metabolism, pathology)
• Female
• Gene Deletion
• Gene Expression Regulation (genetics)
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• Intracranial Hypertension (genetics, metabolism, pathology)
• Mice
• Mice, Knockout
• Neuroglia (metabolism, pathology)
• Time Factors
• Water Intoxication (genetics, metabolism, pathology)
• Water-Electrolyte Balance (genetics)