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First published online December 14, 2007
Journal of Experimental Biology 211, iv-a (2008)
Copyright © 2008 The Company of Biologists Limited
doi: 10.1242/jeb.010751
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Outside JEB

STOPPING THE CLOCK

Jonathan A. W. Stecyk

University of Oslo jonathan.stecyk{at}imbv.uio.no


Figure 1

Hibernation is a fascinating, yet enigmatic, physiological phenomenon utilized by some mammals to successfully cope with the extreme conditions of a harsh season such as winter. During the inhospitable season, hibernating animals repeatedly alternate between brief periods at normal body temperature (Tb) of 37°C (known as euthermia) and a state of torpor when Tb drops to as low as 5–10°C and biological processes such as heart rate, respiration rate, immune and renal functions and neural activity are slowed to a minimum. This strategy allows for substantial energy savings, enabling the organism to survive the severe conditions.

Normally, an animal's circadian system serves to coordinate internal biological processes with each other and the environment to ensure health and survival. However, it has long been debated whether the circadian clock continues to function in hibernating mammals. Numerous studies have indirectly investigated this question by examining several different markers of a functioning circadian clock in hibernating animals. But, results have been conflicting; with some studies contending the clock continues to function, whereas others claim it stops.

Dr Paul Pévet's group at Université Louis Pasteur, Paris, reasoned that the best way to resolve whether or not the circadian clock continues to operate during hibernation would be to directly examine whether the `core clockwork machinery' (i.e. the molecular mechanisms underlying the ticking of the clock) still functioned as normal during hibernation. The team explains that circadian oscillations result from the recurrent expression of so-called clock genes in a region of the brain known as the suprachiasmatic nucleus, or SCN for short. These clock genes interact in complex, interlocked transcription/translation feedback loops, resulting in significant day/night differences in gene expression. Therefore, the team surmised that a stopped clock during hibernation would be reflected by a loss of the rhythmic expression of the clock genes.

Employing the European hamster (Cricetus cricetus), a well-defined hibernator, as a model species, the researchers examined the expression levels of three clock genes and another clock-controlled gene in euthermic and hibernating animals. As expected, the researchers observed that in non-hibernating hamsters, significant day/night changes occurred in the expression of the clock genes. In contrast, in hibernating hamsters exhibiting torpor, the day/night differences in gene expression disappeared. Rather, the expression of the clock genes in the brain's SCN remained constant. Most importantly, the team observed that the oscillations in clock gene expression reoccurred during the inter-torpor periods of euthermia.

Overall, the authors argue that their novel data provide strong evidence that the molecular circadian clock stops `ticking', at least in the European hamster, during the torpor periods of hibernation. The teams' next steps will be to elucidate the mechanisms by which the stopping of the clock occurs and whether the phenomenon is species and/or temperature specific.

References

Revel, F. G., Herwig, A., Garidou, M.-L., Dardente, H., Menet, J. S., Masson-Pévet, M., Simonneaux, V., Saboureau, M. and Pévet, P. (2007). The circadian clock stops ticking during deep hibernation in the European hamster. Proc. Natl. Acad. Sci. USA 104,13816 -13820.[Abstract/Free Full Text]





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