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SLEEP AND TEMPERATURE REGULATION

Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder

¹Department of Pharmacy, Kumamoto University Hospital, and ²Department of Child Development, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; ³Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; and ⁴Kyusyu Clinical Pharmacology Research Clinic, Fukuoka, Japan

Submitted 23 February 2005 ; accepted in final form 13 June 2005

In recent years, circadian rhythm sleep disorders in humans have been increasing. Clinical features characteristic of this disorder are well known, but the specific causes remain unknown. However, various derangements of circadian expression of the clock gene are a probable cause of this disease. We have attempted to elucidate the relationship between the expression of the clock genes in whole blood cells and the clinical features characteristic of this disorder. In this study, we indicate the daily expression of clock genes period (Per) 1, 2, 3, Bmal1, and Clock in whole blood cells in 12 healthy male subjects. The peak phase of Per1, Per2, and Per3 appeared in the early morning, whereas that of Bmal1 and Clock appeared in the midnight hours. Furthermore, in one patient case with circadian rhythm sleep disorder, we observed variations of the peak phase in clock genes by treatments such as light therapy, exercise therapy, and medicinal therapy. This study suggested that the monitoring of human clock genes in whole blood cells, which may be functionally important for the molecular control of the circadian pacemaker as well as in suprachiasmatic nucleus, might be useful to evaluate internal synchronization.

circadian pacemaker; internal synchronization

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