Control mechanism of biological clocks in relation to mood, behavior and sleep disorders and Their treatments.

1.在我们的临床研究中，对于昼夜节律睡眠障碍的发病机制，Uchiyama和Yamada报告如下：在昏暗的光线条件下，每小时评估血清褪黑激素、皮质醇和促甲状腺激素（TSH）的浓度，持续26小时。与对照组相比，DSPS患者的激素节律明显延迟，而24小时激素分泌量和激素节律之间的相位关系在两组之间没有差异。他们假设DSPS患者的睡眠阶段延迟是昼夜节律起搏器的阶段延迟的结果，这表明昼夜节律钟的阶段延迟是造成这种疾病的原因。在哺乳动物中，生物钟相关基因如Per 1/2/3、Cry 1/2、clock等在主生物钟所在的achia -asmatic核中表达，形成转录/翻译反馈回路，产生昼夜节律。Ebisawa等人报道了…More Per3基因多态性与延迟睡眠阶段综合征（DSPS）有关。据报道，下丘脑泌素在食物摄入、能量稳态和维持警觉性水平中发挥重要作用，orexin敲除（KO）小鼠表现出食物摄入行为减弱。Shibata等在对照动物中观察到含有orexin和Fos蛋白神经元的细胞数量高峰出现在夜间。然而，摄食时间被限制在白天，摄食节律的相位提前。然而，在KO小鼠中，没有表现出阶段提前，这表明食欲素参与了食物摄入节奏。前列腺素（PG） D2是最有效的促进睡眠的物质之一。Urade等人报道PGD2诱导的睡眠可被腺苷A2a受体（A2AR）拮抗剂抑制，提示A2AR可能介导PGD2的睡眠促进作用。在本研究中，他们利用基因操纵的A2AR敲除（KO）小鼠进一步探索腺苷受体亚型参与PGD2的致睡作用。结果提示A2AR的激活主要参与腺苷的促睡作用，进一步实验表明腺苷A2AR缺乏会减弱PGD2的促睡作用。少

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 … More 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