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Am J Physiol Regul Integr Comp Physiol (June 16, 2005). doi:10.1152/ajpregu.00126.2005
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Submitted on February 23, 2005
Accepted on June 13, 2005

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

Mieko Takimoto1, Akinobu Hamada1, Akemi Tomoda2, Shigehiro Ohdo3, Takafumi Ohmura1, Hisao Sakato2, Junko Kawatani2, Takako Jodoi2, Hiroo Nakagawa3, Hideyuki Terazono3, Satoru Koyanagi3, Shun Higuchi3, Miyuki Kimura4, Hiroshi Tukikawa4, Shin Irie4, Hideyuki Saito1*, and Teruhisa Miike2

1 Department of Pharmacy, Kumamoto University Hospital, Kumamoto, Japan
2 Department of Child Development, Kumamoto University, Kumamoto, Japan
3 Department of Clinical Pharmacokinetics, Kyushu University, Fukuoka, Japan
4 Kyusyu Clinical Pharmacology Research Clinic, Fukuoka, Japan

* To whom correspondence should be addressed. E-mail: saitohide{at}fc.kuh.kumamoto-u.ac.jp.

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, Clock in whole blood cells in twelve healthy men subjects. The peak phase of Per1, 2, and 3 appeared in the early morning, whereas that of Bmal1 and Clock in the midnight. 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 SCN, might be useful to evaluate internal synchronization.




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