Keywords
Acetazolamide, Aquaporins, Choroid plexus, Hydrocephalus
Abstract
Acetazolamide (AZA), the only drug approved for treatment of hydrocephalus, is effective in only 25-30% of patients while its effect on fluid flow in the choroid plexus (CP) is unknown. The drug reversibly inhibits Aquaporin 4 (AQP4), the most highly expressed „water pore‟ in the brain, and it is postulated that it reduces cerebrospinal fluid (CSF) production by modulating AQP1 (mostly found in the apical membrane of the CP). In this study, we sought to elucidate the effect of AZA on AQP1 and fluid flow in CP. Primary CP culture from p10 Sprague-Dawley rats and TRCSF-B cell line were grown on Transwell permeable supports, treated with 100µM AZA or 100µM Vinpocetine (previously shown to increase AQP1 levels), and tested by: a) Fluid assays using TRITC-labeled Dextran to assay direction and extent of fluid flow; b) Immunoblot, Immunocytochemistry (ICC), and RT-PCR for AQP1 expression. Immnoblots and ICC analyses showed that AQP1 protein levels decrease in a delayed manner (lowest at 12 hours) with AZA treatment. The reduction in AQP1 protein was transient and preceded by a reduction in mRNA levels (lowest at 6 hours). Transwell fluid assays indicate a shift in fluid flow at 2 hours, prior to the changes in AQP1 mRNA or protein. Alteration of fluid flow by AZA (in both primary culture and TR-CSFB) is similar to Vinpocetine‟s effect in primary culture. Together with druginduced alterations in AQP1 levels, these data suggest independent mechanisms behind fluid flow and AQP1 expression.
Notes
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Graduation Date
2010
Semester
Fall
Advisor
Chan, Sic L.
Degree
Master of Science (M.S.)
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Degree Program
Biotechnology
Format
application/pdf
Identifier
CFE0003501
URL
http://purl.fcla.edu/fcla/etd/CFE0003501
Language
English
Release Date
June 2016
Length of Campus-only Access
5 years
Access Status
Masters Thesis (Open Access)
Subjects
Dissertations, Academic -- Medicine, Medicine -- Dissertations, Academic
STARS Citation
Ameli, Pouya Alexander, "Acetazolamide-induced Decrease Of Apical Fluid Flow In Choroid Plexus Is Independent Of The Concomitant Changes In Aquaporin-1 Expression" (2010). Electronic Theses and Dissertations. 1584.
https://stars.library.ucf.edu/etd/1584