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"ACETAZOLAMIDE-INDUCED DECREASE OF APICAL FLUID FLOW IN CHOROID PLEXUS IS INDEPENDENT OF THE CONCOMITANT CHANGES IN AQUAPORIN-1 EXPRESSION"

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Date Issued:
2010
Abstract/Description:
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 100uM AZA or 100uM 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 drug-induced alterations in AQP1 levels, these data suggest independent mechanisms behind fluid flow and AQP1 expression.
Title: "ACETAZOLAMIDE-INDUCED DECREASE OF APICAL FLUID FLOW IN CHOROID PLEXUS IS INDEPENDENT OF THE CONCOMITANT CHANGES IN AQUAPORIN-1 EXPRESSION".
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Name(s): Ameli, Pouya, Author
Chan, Sic, Committee Chair
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2010
Publisher: University of Central Florida
Language(s): English
Abstract/Description: 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 100uM AZA or 100uM 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 drug-induced alterations in AQP1 levels, these data suggest independent mechanisms behind fluid flow and AQP1 expression.
Identifier: CFE0003501 (IID), ucf:48935 (fedora)
Note(s): 2010-12-01
M.S.
Medicine, Burnett College of Biomedical Sciences
Masters
This record was generated from author submitted information.
Subject(s): hydrocephalus
choroid plexus
aquaporin
acetazolamide
fluid flow
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0003501
Restrictions on Access: campus 2016-06-01
Host Institution: UCF

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