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Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag
Silke Kiessling, … , Gregor Eichele, Henrik Oster
Silke Kiessling, … , Gregor Eichele, Henrik Oster
Published June 23, 2010
Citation Information: J Clin Invest. 2010;120(7):2600-2609. https://doi.org/10.1172/JCI41192.
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Research Article Article has an altmetric score of 12

Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag

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Abstract

Jet lag encompasses a range of psycho- and physiopathological symptoms that arise from temporal misalignment of the endogenous circadian clock with external time. Repeated jet lag exposure, encountered by business travelers and airline personnel as well as shift workers, has been correlated with immune deficiency, mood disorders, elevated cancer risk, and anatomical anomalies of the forebrain. Here, we have characterized the molecular response of the mouse circadian system in an established experimental paradigm for jet lag whereby mice entrained to a 12-hour light/12-hour dark cycle undergo light phase advancement by 6 hours. Unexpectedly, strong heterogeneity of entrainment kinetics was found not only between different organs, but also within the molecular clockwork of each tissue. Manipulation of the adrenal circadian clock, in particular phase-shifting of adrenal glucocorticoid rhythms, regulated the speed of behavioral reentrainment. Blocking adrenal corticosterone either prolonged or shortened jet lag, depending on the time of administration. This key role of adrenal glucocorticoid phasing for resetting of the circadian system provides what we believe to be a novel mechanism-based approach for possible therapies for jet lag and jet lag–associated diseases.

Authors

Silke Kiessling, Gregor Eichele, Henrik Oster

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Figure 5

Shifting corticosterone rhythms prior to jet lag affects behavioral resetting kinetics in a phase-advance paradigms.

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Shifting corticosterone rhythms prior to jet lag affects behavioral rese...
(A and B) Advanced and delayed corticosterone excretion rhythms of WT METD (A) and METN (B) mice after 16 days of MET treatment. The direction of the shift of the corticosterone peak time prior to jet lag in treated mice in comparison to the peak time in SALD, SALN, and UT control mice (n = 5) is indicated (ΔZTmax). (C and D) Representative double-plotted actograms of SALD and METD mice (C) and SALN and METN mice (D) 2 weeks before and 2 weeks after a 6-hour phase advance of the LD cycle. Time and duration of MET treatment is shown by red bars. Dark phases are denoted by gray shading. (E and F) Resetting kinetics of activity onsets of METD and SALD mice (E), METN and SALN mice (F), and UT controls. Resetting kinetics of injected animals differed significantly from that of saline-treated animals (P < 0.0001, METD vs. SALD; P = 0.0003, METN vs. SALN; n = 6 per group). All values are average ± SEM.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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