Altered cellular localization of aquaporin-1 in experimental hydrocephalus in mice and reduced ventriculomegaly in aquaporin-1 deficiency.

Abstract

Hydrocephalus is a pathological accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles that constitutes a significant cause of neurological morbidity and mortality. Surgical treatment involving shunt placement is associated with a high failure rate and complications due to infection, motivating the development of alternative, non-surgical therapies. Here, we investigated the role in hydrocephalus of water channel aquaporin-1 (AQP1), which is expressed at the apical membrane of choroid plexus epithelium and is believed to facilitate CSF production. AQP1 expression and subcellular localization were studied in a kaolin-induced hydrocephalus model in mice and the effect AQP1 deficiency on the severity of hydrocephalus was determined. While total choroidal AQP1 protein was not significantly altered in hydrocephalus, ~50% of AQP1 protein was redistributed from the apical membrane to intracellular vesicles. We found that the ventricular size in AQP1-deficient mice was smaller than in wild-type mice, both at baseline and following hydrocephalus. The reduced plasma membrane AQP1 localization following kaolin-induced hydrocephalus, which involves endocytosis, may be a compensatory mechanism to reduce CSF secretion. The reduced ventricular size in AQP1-deficient mice following kaolin-induced hydrocephalus suggests AQP1 inhibition or down-regulation as a potential adjunctive treatment for hydrocephalus.

• Authors: Dongwei Wang, Marko Nykanen, Nan Yang, David Winlaw, Kathryn North, A S Verkman, Brian Kenneth Owler
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 46 Issue 1 Pg. 318-24 (Jan 2011) ISSN: 1095-9327 [Electronic] United States
• PMID: 21040788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Aquaporin 1
• Kaolin

Topics

• Animals
• Aquaporin 1 (genetics, metabolism)
• Cerebral Ventricles (pathology)
• Cerebrospinal Fluid (metabolism)
• Choroid Plexus (cytology, metabolism, pathology)
• Cytoplasmic Vesicles (metabolism, ultrastructure)
• Humans
• Hydrocephalus (chemically induced, pathology, physiopathology)
• Kaolin (pharmacology)
• Mice
• Mice, Knockout
• Microscopy, Immunoelectron