Differential resynchronisation of circadian clock gene expression within the suprachiasmatic nuclei of mice subjected to experimental jet lag.
Disruption of the circadian timing system arising from travel between time zones ("jet lag") and rotational shift work impairs mental and physical performance and severely compromises long-term health. Circadian disruption is more severe during adaptation to advances in local time, because the circadian clock takes much longer to phase advance than delay. The recent identification of mammalian circadian clock genes now makes it possible to examine time zone adjustments from the perspective of molecular events within the suprachiasmatic nucleus (SCN), the principal circadian oscillator. Current models of the clockwork posit interlocked transcriptional/post-translational feedback loops based on the light-sensitive Period (Per) genes and the Cryptochrome (Cry) genes, which are indirectly regulated by light. We show that circadian cycles of mPer expression in the mouse SCN react rapidly to an advance in the lighting schedule, whereas rhythmic mCry1 expression advances more slowly, in parallel to the gradual resetting of the activity-rest cycle. In contrast, during a delay in local time the mPer and mCry cycles react rapidly, completing the 6 hr shift together by the second cycle, in parallel with the activity-rest cycle. These results reveal the potential for dissociation of mPer and mCry expression within the central oscillator during circadian resetting and a differential molecular response of the clock during advance and delay resetting. They highlight the indirect photic regulation of mCry1 as a potentially rate-limiting factor in behavioral adjustment to time zone transitions.
Medical Research Council Laboratory of Molecular Biology, Division of Neurobiology, University of Cambridge, Cambridge, CB2 2QH, United Kingdom.
A B
AB
Reddy
M D
MD
Field
E S
ES
Maywood
M H
MH
Hastings
D000704:Analysis of Variance; D000818:Animals; D001683:Biological Clocks; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D056931:Cryptochromes; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D020179:Jet Lag Syndrome / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010507:Periodicity; D017440:Photoperiod; D017956:Photoreceptor Cells, Invertebrate; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D013493:Suprachiasmatic Nucleus / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C119828:cry protein, Drosophila