A circadian clock regulates efflux by the blood-brain barrier in mice and human cells

Shirley L. Zhang (), Nicholas F. Lahens, Zhifeng Yue, Denice M. Arnold, Peter P. Pakstis, Jessica E. Schwarz and Amita Sehgal ()
Additional contact information
Shirley L. Zhang: Perelman School of Medicine at the University of Pennsylvania
Nicholas F. Lahens: University of Pennsylvania
Zhifeng Yue: Perelman School of Medicine at the University of Pennsylvania
Denice M. Arnold: Perelman School of Medicine at the University of Pennsylvania
Peter P. Pakstis: Perelman School of Medicine at the University of Pennsylvania
Jessica E. Schwarz: Perelman School of Medicine at the University of Pennsylvania
Amita Sehgal: Perelman School of Medicine at the University of Pennsylvania

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract The blood-brain barrier (BBB) is critical for neural function. We report here circadian regulation of the BBB in mammals. Efflux of xenobiotics by the BBB oscillates in mice, with highest levels during the active phase and lowest during the resting phase. This oscillation is abrogated in circadian clock mutants. To elucidate mechanisms of circadian regulation, we profiled the transcriptome of brain endothelial cells; interestingly, we detected limited circadian regulation of transcription, with no evident oscillations in efflux transporters. We recapitulated the cycling of xenobiotic efflux using a human microvascular endothelial cell line to find that the molecular clock drives cycling of intracellular magnesium through transcriptional regulation of TRPM7, which appears to contribute to the rhythm in efflux. Our findings suggest that considering circadian regulation may be important when therapeutically targeting efflux transporter substrates to the CNS.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20795-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20795-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20795-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().