# Drug Transport Mechanisms at the Blood-CSF Barrier and Effect of Aging

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $190,309

## Abstract

Research Summary
Brain disorders, especially age-related neurological diseases, constitute a major public health problem in the
developed world. Despite the urging needs for new and more effective drugs to treat brain diseases,
development of CNS drugs remains challenging. To exert their therapeutic effects, CNS-targeted drugs must
cross the brain-blood barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) and maintain minimal
effective concentrations in the brain. The BBB and BCSFB are not only physical barriers but also express a
spectrum of multispecific drug transporters to actively remove drugs and other xenobiotics from the brain. The
choroid plexus epithelial (CPE) cells forming the BCSFB play an essential role in brain removal of drugs and
metabolites through secretion of the CSF and active transport of solutes from the CSF into the blood circulation.
Nevertheless, little is known regarding the molecular and cellular mechanisms governing drug transport
show marked morphological and functional
changes
developed a live tissue imaging approach in isolated murine
choroid plexus to analyze organic anion and cation transport processes in CPE cells. Our
processes at the BCSFB. Furthermore, the CPE cells are known to
changes during aging but
it is unknown if these age-dependent impact the expression and activity of
transporters at the BCSFB. Our laboratory recently
preliminary studies
suggest that large amphipathic organic anions (OAs) are rapidly cleared from the CSF side into the blood
capillary side by a highly functional BCSFB transport system likely consisting of organic anion transporting
polypeptides (Oatps) at the apical membrane and multidrug resistance-associated proteins (Mrps) at the
basolateral membrane. We hypothesize that Oatps mediate the first and rate-limiting step in the transport of
structurally diverse amphipathic OAs across the BCSFB and that the expression and activity of Oatps and Mrps
at the BCSFB are regulated by aging. The goals of this application are to determine the functional characteristics
of the BCSFB amphipathic OA transport system, define the role of Oatp1a transporters in BCSFB transport, and
explore age-dependent changes in transporter expression and function at the BCSFB. The proposed studies
will build a functional and mechanistic framework for a major xenobiotic clearance pathway at the BCSFB and
pave the way for future studies to investigate the impact of BCSFB transporters and aging on CNS drug
disposition, pharmacokinetics and pharmacodynamics.

## Key facts

- **NIH application ID:** 10492591
- **Project number:** 5R21AG071827-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Joanne Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,309
- **Award type:** 5
- **Project period:** 2021-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492591

## Citation

> US National Institutes of Health, RePORTER application 10492591, Drug Transport Mechanisms at the Blood-CSF Barrier and Effect of Aging (5R21AG071827-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10492591. Licensed CC0.

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