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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

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 1

Behavioral entrainment during jet lag.

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Behavioral entrainment during jet lag.
(A) Representative double-plotted...
(A) Representative double-plotted actogram of a mouse before and after 6-hour LD phase advance applied at day 1. Tick marks represent wheel running activity; gray shading denotes dark lighting conditions. (B) Average onset of mice (n = 9) during jet lag. PS50 (4.0 ± 0.1 days) was defined as the time at which half the phase shift was completed. All values are average ± SEM.
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