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VOLUME 30, ISSUE 11


Circadian Rhythms of Melatonin, Cortisol, and Clock Gene Expression During Simulated Night Shift Work

Francine O. James, PhD1,2; Nicolas Cermakian, PhD2,3; Diane B. Boivin, MD, PhD1,3

1Centre for Study and Treatment of Circadian Rhythms, Douglas Mental Health University Institute, Montréal, Québec, Canada; 2Laboratory of Molecular Chronobiology, Douglas Mental Health University Institute, Montréal, Québec, Canada; 3Department of Psychiatry, McGill University, Montréal, Québec, Canada



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Study Objectives:

The synchronization of peripheral circadian oscillators in humans living on atypical sleep/wake schedules is largely unknown. In this night shift work simulation, we evaluate clock gene expression in peripheral blood mononuclear cells (PBMCs) relative to reliable markers of the central circadian pacemaker.

Design:

Participants were placed on a 10-hr delayed sleep/wake sched-ule simulating nighttime work followed by a daytime sleep episode.

Setting:

Baseline, intermediate and final circadian evaluations were per-formed in the temporal isolation laboratory.

Participants:

Five healthy candidates, 18-30 years.Interventions: Polychromatic white light of (mean ±SEM) 6,036 ±326 lux (~17,685 ±955 W/m2) during night shifts; dim light exposure after each night shift; an 8-hr sleep/darkness episode beginning 2 hrs after the end of each night shift.

Measurements:

Melatonin and cortisol in plasma; clock genes HPER1, HPER2 and HBMAL1 RNA in PBMCs.

Results:

Following 9 days on the night schedule, hormonal rhythms were adapted to the shifted schedule. HPER1 and HPER2 expression in PBMCs displayed significant circadian rhythmicity, which was in a con-ventional relationship with the shifted sleep/wake schedule. Changes in the pattern of clock gene expression were apparent as of 3 days on the shifted sleep/wake schedule.

Conclusions:

This preliminary study is the first documentation of the ef-fects of a shifted sleep/wake schedule on the circadian expression of both peripheral circadian oscillators in PBMCs and centrally-driven hormonal rhythms. In light of evidence associating clock gene expression with tissue function, the study of peripheral circadian oscillators has important impli-cations for understanding medical disorders affecting night shift workers.
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