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报道如下：在暗光条件下每小时测定血清褪黑素、皮质醇和促甲状腺激素(TSH)浓度。与对照组相比，DPS患者的激素节律明显延迟，而24小时的激素分泌量和激素节律之间的时相关系在两组间无明显差异。他们推测，DPS患者的睡眠时相延迟是昼夜节律起搏器相位延迟的结果，这表明生物钟中的时相延迟是导致这种紊乱的原因。2.在哺乳动物中，时钟相关基因，如PER 1/2/3、Cry 1/2、Clock等在主昼夜节律的位置--视上核中表达，并形成转录/翻译反馈环来产生昼夜节律性。EBisawa等人的研究成果。据报道，…基因的多态更多的PER3基因与睡眠延迟综合征有关。3.据报道，下丘脑泌素在食物摄入、能量平衡和维持警觉水平方面发挥着重要作用，增食欲素基因敲除(KO)的小鼠表现出进食行为的减弱。柴田等人。对照动物体内同时含有食欲素和Fos蛋白神经元的细胞数高峰出现在夜间，但摄食时间受到白天的限制，摄食节律的相位提前。然而，在KO小鼠中，并没有表现出相位推进，这表明增食欲素参与了摄食节律。4.前列腺素(PG)D2是最有效的促进睡眠的物质之一。Urade等人。已报道的PGD2诱导的睡眠可被腺苷A2a受体(A2AR)拮抗剂抑制，提示A2AR可能介导了PGD2的睡眠促进作用。在目前的研究中，他们利用基因操作的A2AR基因敲除(KO)小鼠来进一步探讨腺苷受体亚型参与PGD2的催眠效应。结果表明，A2AR的激活主要参与了腺苷的催眠作用，进一步的实验表明，腺苷A2AR缺乏减弱了PGD2的催眠作用。较少

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