Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag.
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.
Kiessling
Silke
S
Department Genes and Behavior, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Eichele
Gregor
G
Oster
Henrik
H
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000502:physiology*; D020179:Jet Lag Syndrome / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013997:Time Factors
D005938:Glucocorticoids