权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Determine transporters at the blood-brain barrier relevant for homeostatic sleep

确定与稳态睡眠相关的血脑屏障转运蛋白

基本信息

批准号：
10548484
负责人：
Shirley Zhang
金额：
$ 2.4万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10548484
关键词：
ATP phosphohydrolase Address Affect Alpha Rhythm Animal Behavior Behavior Behavioral Binding Biological Assay Biological Process Blood - brain barrier anatomy Brain Cells Cerebrovascular Disorders Chronic Chronotherapy Circadian Rhythms Data Disease model Drosophila genus Endothelium Event Future Goals Health Human Impairment Inflammatory Intervention Ions Ligands Mammals Measurement Measures Mediating Metabolic syndrome Molecular Mus Nervous System Physiology Neurophysiology - biologic function Obesity Organism Periodicity Peripheral Permeability Publishing RNA Interference Regulation Role Sleep Sleep Deprivation Stimulus Structure Tissues Vitamins Work Xenobiotics base behavior influence blood-brain barrier permeabilization circadian circadian pacemaker improved insight knock-down lipophilicity metabolomics molecular clock mouse model mutant novel parent grant sleep behavior sleep regulation systemic inflammatory response

项目摘要

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 regulation of endogenous ligands and its relevance to behaviors such as sleep. Based on published and preliminary data, we hypothesize that the BBB clock influences behavior through transporter-regulated endogenous ligands. To pursue these aims, we will use a combination of molecular assays (qPCR, intracellular ion measurements, metabolomics) and behavioral sleep assays. Successful completion of this project will offer important advances in understanding the effects of the BBB transport and sleep. First, it will provide new insights into the regulation of sleep behavior. Second, 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.

项目总结/文摘