PloS one, 2011-08, Vol.6 (8), p.e23982-e23982
2011
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- Autor(en) / Beteiligte
- Titel
- Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene expression
- Ist Teil von
- PloS one, 2011-08, Vol.6 (8), p.e23982-e23982
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3β antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0023982Titel-ID: cdi_plos_journals_1308202785
- Format
- –
- Schlagworte
- Abnormalities, Analysis, Animals, Antidepressants, Biology, BMAL1 protein, Bone marrow, Chromatin, Circadian rhythm, Circadian Rhythm Signaling Peptides and Proteins - drug effects, Circadian Rhythm Signaling Peptides and Proteins - physiology, Circadian rhythms, CLOCK Proteins - drug effects, CLOCK Proteins - physiology, Cryptochromes, Drug dosages, Epigenetics, Excitatory Amino Acid Antagonists - pharmacology, Gene expression, Gene Expression Regulation - physiology, Genes, Immunoprecipitation, Ketamine, Ketamine - pharmacology, Kinases, Lithium, Machinery and equipment, Mammals, Medicine, Mental depression, Metabolism, Mice, Mode of action, Molecular machines, Mood, Period 2 protein, Period Circadian Proteins - genetics, Pharmacology, Physiology, Poly(ADP-ribose) Polymerases - drug effects, Poly(ADP-ribose) Polymerases - physiology, Psychiatry, Regulators, Rodents, Sleep, Species Specificity, Transcription (Genetics), Transcription activation, Trends