Vol 9, No 3 - Chronobiology in Psychiatry
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iological clocks are devices that can measure time in the absence of environmental timing cues, such as changes in light intensity, temperature, or humidity.1 The discovery of circadian clocks dates back to 1729, when the French astronomer Jean Jacques Ortous de Mairan observed that mimosa plants continued to open and close their leaves in a daily manner when kept in the absence of sunlight.2 Obviously, other environmental oscillations such as daily temperature fluctuations could have driven the  cyclic  leaf  openings  in  de  Mairan’s  experiment, thereby challenging his conclusion about the existence of a mimosa clock. However, in 1832 the Swiss physician and botanist Augustin Pyrame de Candolle demonstrated that in constant light mimosa plants opened and closed their leaves with a cycle of 22 hours rather than 24 hours.3 This observation provided irrefutable evidence that the leaf movement rhythm was not merely driven by cyclic environmental cues depending on the earth’s rotation, but by a self-sustained biological clock. Incidentally,“cir- cadian” is derived from the Latin words “circa diem” and indicates that circadian clocks can measure days only approximately. Hence, the phase of circadian oscillators must be corrected daily to stay in resonance with geo- physical time. The photoperiod (ie, daily variations in light intensity) is the primary Zeitgeber for the synchro- nization of circadian clocks.1,4-6 Since the discovery of endogenous timekeepers in plants, such devices have been found in virtually all investigated B a s i c   r e s e a r c h The daily timing of gene expression and physiology in mammals Ueli Schibler, PhD B Keywords: circadian clock; suprachiasmatic nucleus; peripheral oscillator; PAR bZip transcription factor; albumin d-element-binding protein; hepatic leukemia factor; thyrotroph embryonic factor; xenobiotic detoxification Author affiliations: Department of Molecular Biology and National Center of Competence in Research  “Frontiers  in Genetics” Sciences III,  University  of Geneva, Switzerland   Address  for  correspondence:  Department  of  Molecular  Biology  and  National Center of Competence in Research “Frontiers in Genetics,” Sciences III, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland (e-mail: Ueli.Schibler@molbio.unige.ch) Mammalian  behavior  and  physiology  undergo  daily rhythms that are coordinated by an endogenous circa- dian timing system. This system has a hierarchical struc- ture,  in  that  a  master  pacemaker,  residing  in  the suprachiasmatic nucleus of the ventral hypothalamus, synchronizes peripheral oscillators in virtually all body cells. While the basic molecular mechanisms generating the daily rhythms are similar in all cells, most clock out- puts are cell-specific. This conclusion is based on genome- wide transcriptome profiling studies in several tissues that have revealed hundreds of rhythmically expressed genes. Cyclic gene expression in the various organs gov- erns overt rhythms in behavior and physiology, encom- passing sleep-wake cycles, metabolism, xenobiotic detox- ification, and cellular proliferation. As a consequence, chronic perturbation of this temporal organization may lead to increased morbidity and reduced lifespan. © 2007, LLS SAS Dialogues Clin Neurosci. 2007;9:257-272. Copyright © 2007 LLS SAS.  All rights reserved www.dialogues-cns.org