EBISAWA Takashi Saitama University of Medical Science, Lecturer, 医学部, 講師 (00201369)
URADA Yoshihiro Osaka Bioscience Institute Department of Molecular Biology, manager, 第二研究部, 部長 (10201360)
SHIBATA Shigenobu Waseda University Department of Human Science, Professor, 人間科学部, 教授 (10162629)
山田 尚登 北島津病院, 副院長 (50166724)
UCHIYAMA Macoto National Center of Neurology and Psychiatry of National Institute of Mental Health, manager, 精神生理部, 部長 (20221111)
|Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2003: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2002: ¥8,900,000 (Direct Cost: ¥8,900,000)
1.In our clinical investigations, for pathogenesis of circadian rhythm sleep disorders, Uchiyama and Yamada reported as follows: Concentrations of serum melatonin, cortisol, and thyroid-stimulating hormone (TSH) were assessed every hour for 26h under dim light condition. The hormonal rhythms were significantly delayed in patients with DSPS compared with controls, whereas the 24-h amounts of hormonal secretions and the phase relations between the hormonal rhythms did not differ between the groups. They postulate that sleep-phase delay in patients with DSPS is a consequence of the phase delay of the circadian pacemaker, suggesting that phase delay in the circadian clock is responsible for this disorder.
2.In mammals, clock related genes, such as Per 1/2/3, Cry 1/2, Clock, etc. are expressed in suprachi-asmatic nucleus, the site of a master circadian clock, and form transcriptional/translational feed-Back Loops to generate circadian rhythmicity. Ebisawa et al. reported that polymorphism in
Per3 gene is associated with delayed sleep phase syndrome (DSPS).
3.The importance of hypocretin has been reported to play an important role in food intake, energy homeostasis and maintenance of vigilance level, and orexin knock out (KO) mice showed attenuated food intake behavior. Shibata et al. have observed in control animals the peak time of cell numbers containing both orexin and Fos protein neurons appeared during night time.
However, their feeding time was restricted in daytime, the phase advance of food intake rhythm was observed. However, in KO mice, did not show phase advance, which indicates orexin is involved in food intake rhythm.
4.Prostaglandin (PG) D2 is one of the most Potent sleep promoting substances. Urade et al. reported PGD2-induced sleep can be inhibited by an adenosine A2a receptor (A2AR) antagonist, suggesting that A2AR probably mediates the sleep promoting effect of PGD2. In the present study, they employed the gene-manipulated A2AR knockout (KO) mice to further explore the involvement of adenosine receptor subtypes in the somnogenic effect of PGD2. The results suggested that activation of A2AR was mainly involved in sleep promotion effect of adenosine and further experiment indicates that adenosine A2AR deficiency attenuates the somnogenic effect of PGD2. Less