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

作者：Wang Dongwei; Nykanen Marko; Yang Nan; Winlaw David; North Kathryn; Verkman A S; Owler Brian Kenneth^*

来源：Molecular and Cellular Neuroscience, 2011, 46(1): 318-324.

DOI：10.1016/j.mcn.2010.10.003

• Hydrocephalus
• Aquaporins
• Choroid plexus
• Cerebrospinal fluid

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, similar to 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.

• 出版日期2011-1-11