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

Cell, ISSN: 0092-8674, Vol: 173, Issue: 1, Page: 130-139.e10
2018
  • 151
    Citations
  • 0
    Usage
  • 365
    Captures
  • 4
    Mentions
  • 4
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    151
  • Captures
    365
  • Mentions
    4
    • News Mentions
      3
      • News
        3
    • References
      1
      • Wikipedia
        1
  • Social Media
    4
    • Shares, Likes & Comments
      4
      • Facebook
        4

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Article Description

Endogenous circadian rhythms are thought to modulate responses to external factors, but mechanisms that confer time-of-day differences in organismal responses to environmental insults/therapeutic treatments are poorly understood. Using a xenobiotic, we find that permeability of the Drosophila “blood”-brain barrier (BBB) is higher at night. The permeability rhythm is driven by circadian regulation of efflux and depends on a molecular clock in the perineurial glia of the BBB, although efflux transporters are restricted to subperineurial glia (SPG). We show that transmission of circadian signals across the layers requires cyclically expressed gap junctions. Specifically, during nighttime, gap junctions reduce intracellular magnesium ([Mg 2+ ]i), a positive regulator of efflux, in SPG. Consistent with lower nighttime efflux, nighttime administration of the anti-epileptic phenytoin is more effective at treating a Drosophila seizure model. These findings identify a novel mechanism of circadian regulation and have therapeutic implications for drugs targeted to the central nervous system.

Bibliographic Details

Zhang, Shirley L; Yue, Zhifeng; Arnold, Denice M; Artiushin, Gregory; Sehgal, Amita

Faculty Opinions Ltd

Biochemistry, Genetics and Molecular Biology

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