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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene expression.

Marina M Bellet1, Marquis P Vawter, Blynn G Bunney

  • 1Center for Epigenetics and Metabolism, School of Medicine, University of California Irvine, Irvine, California, United States of America.

Plos One
|September 3, 2011
PubMed
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Ketamine, an antidepressant, impacts the body's internal clock (circadian rhythm) by affecting key proteins like CLOCK:BMAL1. This discovery offers new avenues for developing antidepressant medications.

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Last Updated: May 29, 2026

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Published on: September 28, 2017

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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
06:53

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Chronobiology

Background:

  • Major mood disorders are associated with circadian rhythm abnormalities.
  • Circadian rhythm disruptions affect sleep, mood, temperature, and hormone levels.

Purpose of the Study:

  • To investigate the effect of ketamine on the molecular machinery of circadian rhythms.
  • To explore ketamine's potential as a pharmacological antidepressant strategy targeting circadian function.

Main Methods:

  • Ectopic expression of CLOCK:BMAL1 regulators in NG108-15 neuronal cells.
  • Assessment of ketamine's dose-dependent effects on transcriptional activation.
  • Analysis of circadian gene expression (Bmal1, Per2, Cry1) following ketamine treatment.
  • Chromatin-immunoprecipitation to evaluate CLOCK:BMAL1 complex recruitment.

Main Results:

  • Ketamine inhibits CLOCK:BMAL1-mediated transcriptional activation in a dose-dependent manner.
  • This inhibition is partially reversed by GSK3β antagonist SB21673.
  • Ketamine reduces the amplitude of circadian transcription for Bmal1, Per2, and Cry1 genes.
  • Ketamine alters CLOCK:BMAL1 complex recruitment to circadian promoters over time.

Conclusions:

  • Ketamine influences the function of the circadian molecular machinery.
  • This provides a novel molecular mechanism of action for ketamine's antidepressant effects.
  • Findings suggest potential new antidepressant pharmacological strategies targeting circadian rhythms.