A role for the adrenal in the synchronization of circadian rhythms in the mouse.

昼夜节律时钟(来自Lat.大约一天)允许有机体预测一天中不同时间相关的环境条件，从而允许对栖息地的最佳适应。昼夜节律系统的破坏--无论是遗传的还是由外部干扰(如时差)造成的--会促进糖尿病、免疫缺陷或癌症等疾病的发展。在分子水平上，生物钟是基于生物钟基因/蛋白质的细胞自主转录反馈环。在哺乳动物中，昼夜节律是按等级系统组织的，中央起搏器位于下丘脑视交叉上核(SCN)，它接收来自视网膜的外部光信息，并在一个称为夹带的过程中重置其他大脑区域和全身的外周时钟。虽然在细胞和组织水平上对昼夜节律计时的分子基础和生理输出进行了广泛的研究，但令人惊讶的是，人们对人体不同生物钟之间的通讯知之甚少。虽然还没有确定一般的时钟重置信号，但似乎涉及体液和神经信号。我们和其他人的研究表明，肾上腺和有节律性分泌的肾上腺皮质时钟调节的糖皮质激素可能在这一背景下发挥重要作用。在本项目中，我们将使用不同的转基因小鼠模型来研究肾上腺时钟的携带，它在体内其他昼夜节律振荡器同步中的功能，以及它在行为节律调节中的作用。我们的发现将有助于开发新的治疗方法，用于治疗由于昼夜节律中断而引起的疾病，例如在时差或轮班工作期间。

Circadian clocks (from the Lat. circa diem - about one day) allow the organism to anticipate time-of-day dependent environmental conditions, thus permitting an optimal adaptation to the habitat. Disruption of the circadian system - either genetic or by external perturbation such as jetlag - promotes the development of diseases such as diabetes, immune deficiency or cancer. At the molecular level circadian clocks are based on cell autonomous transcriptional feedback loops of clock genes/proteins. In mammals circadian timing is organized in a hierarchical system with a central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN) that receives external light information from the retina and resets peripheral clocks in other brain regions and throughout the body in a process called entrainment. While the molecular basics and physiological outputs of circadian timekeeping at the cellular and tissue levels have been extensively studied, remarkably little is known about the communication between different clocks of the body. While no general clock resetting signal has been identified, but both humoral and neuronal signals seem to be involved. Studies from our group and others suggest that the adrenal and the rhythmically secreted, adrenocortical clock regulated glucocorticoids may play an important role in this context.In this project we will use different transgenic mouse models to study the entrainment of the adrenal clock, its function in the synchronization of other circadian oscillators of the body as well as its role in the regulation of behavioral rhythms. Our findings will help to develop new therapeutic approaches for the treatment of disorders resulting from the disruption of circadian timing, e.g. during jetlag or shift work.