# Determining the importance of temporal regulation of the blood-brain barrier

> **NIH NIH R00** · EMORY UNIVERSITY · 2021 · $249,000

## Abstract

Project Summary/Abstract
Circadian clocks are ubiquitous in tissues, regulate many biological functions, and their
misalignment or disruption contributes to deleterious health consequences. Although molecular
underpinning of the circadian clock is well-studied, the role of the clock in tissue-specific biological
functions, such as that of the blood-brain barrier (BBB), is poorly understood. The BBB is an
interface between the vasculature and the brain that both protects the brain from peripheral insults
and allows transports of endogenous molecules. Our recent work has found that the circadian
clock regulates ATPase binding cassette transporter-mediated xenobiotic efflux from the brain.
This proposal examines the mechanisms of BBB circadian clock regulation of endogenous
ligands, its relevance to behaviors such as sleep and feeding, and its perturbation under
conditions of inflammation. I propose that in addition to xenobiotic efflux, the circadian clock in
the BBB regulates endocytosis of particles from brain (Aim 1). Based on published and preliminary
data, I hypothesize that the BBB clock influences behavior through transporter-regulated
endogenous ligands (Aim 2 and 3). Further, I will interrogate the effect of inflammation induced
by either endotoxin or sleep deprivation on the rhythms of the BBB (Aim 4). To pursue these aims,
I will use a combination of molecular assays (qPCR, intracellular ion measurements,
metabolomics), functional bioassays (endocytosis, xenobiotic permeability) and behavioral
assays (sleep, feeding). Successful completion of this project will offer important advances in
understanding both the BBB circadian clock and behavior. First, understanding molecular
mechanism of the BBB clock will further define the role of the clock in gating blood to brain
communication. Second, it will provide new insights into the regulation of behavior. Third, it will
identify novel endogenous sleep-promoting compounds. Understanding the temporal gating of
the BBB and its effects on behavior under pathophysiologic conditions is important for developing
interventions to improve human health.

## Key facts

- **NIH application ID:** 10445428
- **Project number:** 4R00HL147212-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Shirley Zhang
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445428

## Citation

> US National Institutes of Health, RePORTER application 10445428, Determining the importance of temporal regulation of the blood-brain barrier (4R00HL147212-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10445428. Licensed CC0.

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