Altered cellular localization of aquaporin-1 in experimental hydrocephalus in mice and reduced ventriculomegaly in aquaporin-1 deficiency.
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.
Institute for Neuroscience and Muscle Research Children's Hospital at Westmead, Sydney, Australia.
Dongwei
D
Wang
Marko
M
Nykanen
Nan
N
Yang
David
D
Winlaw
Kathryn
K
North
A S
AS
Verkman
Brian Kenneth
BK
Owler
D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D006849:Hydrocephalus / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D007616:Kaolin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron
D051398:Aquaporin 1; D007616:Kaolin