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

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