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

Efflux from mouse brain is highest when mice are active
Circadian clocks in mouse brain endothelium and cultured human endothelial cell culture found to drive TRPM7, a magnesium channel.
Oscillation TRPM7 levels result in fluctuations of intracellular free magnesium levels in brain endothelial cells, driving rhythms in efflux

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A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux

The Drosophila BBB displays a circadian rhythm of permeability
Cyclic efflux driven by a clock in the BBB underlies the permeability rhythm
Circadian control is non-cell-autonomous via gap junction regulation of intracellular magnesium
An anti-seizure drug is more effective when administered at night

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Li Y, Haynes P, Zhang SL, Yue Z, Sehgal A. Ecdysone acts through cortex glia to regulate sleep in Drosophila. eLife. 2023 12:e81723. https://doi.org/10.7554/eLife.81723

Lee Y, Fong SY, Shon J, Zhang SL, Brooks R, Lahens NF, Chen D, Dang CV, Field JM, Sehgal A. Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle. Sci Adv. 2021 Feb;7(7). doi: 10.1126/sciadv.abd2645. Print 2021 Feb. PubMed PMID: 33579708; PubMed Central PMCID: PMC7880601.

Zhang SL, Lahens NF, Yue Z, Arnold DM, Pakstis PP, Schwarz JE, Sehgal A. A circadian clock regulates efflux by the blood-brain barrier in mice and human cells. Nat Commun. 2021 Jan 27;12(1):617. doi: 10.1038/s41467-020-20795-9. PubMed PMID: 33504784; PubMed Central PMCID: PMC7841146.

Sengupta S, Tang SY, Devine JC, Anderson ST, Nayak S, Zhang SL, Valenzuela A, Fisher DG, Grant GR, López CB, FitzGerald GA. Circadian control of lung inflammation in influenza infection. Nat Commun. 2019 Sep 11;10(1):4107. doi: 10.1038/s41467-019-11400-9. PubMed PMID: 31511530; PubMed Central PMCID: PMC6739310.

Cuddapah VA, Zhang SL, Sehgal A. Regulation of the Blood-Brain Barrier by Circadian Rhythms and Sleep. Trends Neurosci. 2019 Jul;42(7):500-510. doi: 10.1016/j.tins.2019.05.001. Review. PubMed PMID: 31253251; PubMed Central PMCID: PMC6602072.

Lee Y, Lahens NF, Zhang S, Bedont J, Field JM, Sehgal A. G1/S cell cycle regulators mediate effects of circadian dysregulation on tumor growth and provide targets for timed anticancer treatment. PLoS Biol. 2019 Apr;17(4):e3000228. doi: 10.1371/journal.pbio.3000228. eCollection 2019 Apr. PubMed PMID: 31039152; PubMed Central PMCID: PMC6490878.

Artiushin G, Zhang SL, Tricoire H, Sehgal A. Endocytosis at the Drosophila blood-brain barrier as a function for sleep. Elife. 2018 Nov 26;7. doi: 10.7554/eLife.43326. PubMed PMID: 30475209; PubMed Central PMCID: PMC6255390.

Rhoades SD, Nayak K, Zhang SL, Sehgal A, Weljie AM. Circadian- and Light-driven Metabolic Rhythms in Drosophila melanogaster. J Biol Rhythms. 2018 Apr;33(2):126-136. doi: 10.1177/0748730417753003. Epub 2018 Jan 21. PubMed PMID: 29355066; PubMed Central PMCID: PMC6692290.

Zhang SL, Yue Z, Arnold DM, Artiushin G, Sehgal A. A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux. Cell. 2018 Mar 22;173(1):130-139.e10. doi: 10.1016/j.cell.2018.02.017. Epub 2018 Mar 8. PubMed PMID: 29526461; PubMed Central PMCID: PMC5866247.

Zhang SL, Bai L, Goel N, Bailey A, Jang CJ, Bushman FD, Meerlo P, Dinges DF, Sehgal A. Human and rat gut microbiome composition is maintained following sleep restriction. Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1564-E1571. doi: 10.1073/pnas.1620673114. Epub 2017 Feb 8. PubMed PMID: 28179566; PubMed Central PMCID: PMC5338418.

Yang E, Zou T, Leichner TM, Zhang SL, Kambayashi T. Both retention and recirculation contribute to long-lived regulatory T-cell accumulation in the thymus. Eur J Immunol. 2014 Sep;44(9):2712-20. doi: 10.1002/eji.201444529. Epub 2014 Jul 1. PubMed PMID: 24894919; PubMed Central PMCID: PMC4177035.

Zhang SL, Wang X, Manna S, Zlotoff DA, Bryson JL, Blazar BR, Bhandoola A. Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice. Blood. 2014 Jul 10;124(2):296-304. doi: 10.1182/blood-2014-01-552794. Epub 2014 May 29. PubMed PMID: 24876562; PubMed Central PMCID: PMC4093685.

Zhang SL, Bhandoola A. Trafficking to the thymus. Curr Top Microbiol Immunol. 2014;373:87-111. doi: 10.1007/82_2013_324. Review. PubMed PMID: 23624945.

Sultana DA, Zhang SL, Todd SP, Bhandoola A. Expression of functional P-selectin glycoprotein ligand 1 on hematopoietic progenitors is developmentally regulated. J Immunol. 2012 May 1;188(9):4385-93. doi: 10.4049/jimmunol.1101116. Epub 2012 Mar 28. PubMed PMID: 22461691; PubMed Central PMCID: PMC3331963.

Gus-Brautbar Y, Johnson D, Zhang L, Sun H, Wang P, Zhang S, Zhang L, Chen YH. The anti-inflammatory TIPE2 is an inhibitor of the oncogenic Ras. Mol Cell. 2012 Mar 9;45(5):610-8. doi: 10.1016/j.molcel.2012.01.006. Epub 2012 Feb 8. PubMed PMID: 22326055; PubMed Central PMCID: PMC3299909.

Zhang SL, Bhandoola A. Losing TREC with age. Immunity. 2012 Feb 24;36(2):163-5. doi: 10.1016/j.immuni.2012.02.005. PubMed PMID: 22365662; PubMed Central PMCID: PMC4026262.

Zlotoff DA, Zhang SL, De Obaldia ME, Hess PR, Todd SP, Logan TD, Bhandoola A. Delivery of progenitors to the thymus limits T-lineage reconstitution after bone marrow transplantation. Blood. 2011 Aug 18;118(7):1962-70. doi: 10.1182/blood-2010-12-324954. Epub 2011 Jun 9. PubMed PMID: 21659540; PubMed Central PMCID: PMC3158723.

Hettiarachchi K, Zhang S, Feingold S, Lee AP, Dayton PA. Controllable microfluidic synthesis of multiphase drug-carrying lipospheres for site-targeted therapy. Biotechnol Prog. 2009 Jul-Aug;25(4):938-45. doi: 10.1002/btpr.214. PubMed PMID: 19455647; PubMed Central PMCID: PMC2782552.

Wondrak GT, Cabello CM, Villeneuve NF, Zhang S, Ley S, Li Y, Sun Z, Zhang DD. Cinnamoyl-based Nrf2-activators targeting human skin cell photo-oxidative stress. Free Radic Biol Med. 2008 Aug 15;45(4):385-95. doi: 10.1016/j.freeradbiomed.2008.04.023. Epub 2008 Apr 26. PubMed PMID: 18482591; PubMed Central PMCID: PMC3710742.

Wang XJ, Sun Z, Villeneuve NF, Zhang S, Zhao F, Li Y, Chen W, Yi X, Zheng W, Wondrak GT, Wong PK, Zhang DD. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 2008 Jun;29(6):1235-43. doi: 10.1093/carcin/bgn095. Epub 2008 Apr 15. PubMed PMID: 18413364; PubMed Central PMCID: PMC3312612.

Sun Z, Zhang S, Chan JY, Zhang DD. Keap1 controls postinduction repression of the Nrf2-mediated antioxidant response by escorting nuclear export of Nrf2. Mol Cell Biol. 2007 Sep;27(18):6334-49. doi: 10.1128/MCB.00630-07. Epub 2007 Jul 16. PubMed PMID: 17636022; PubMed Central PMCID: PMC2099624.