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

肾上腺在小鼠昼夜节律同步中的作用。

• 批准号: 223077205
• 负责人: Professor Dr. Henrik Oster
• 金额: --
• 依托单位: Institut für Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/223077205?language=en
• 关键词: role; adrenal; synchronization; circadian; rhythms

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.

昼夜节律钟（来自Lat。大约一天），使生物体能够预测一天中的时间依赖的环境条件，从而允许对栖息地的最佳适应。昼夜节律系统的破坏--无论是遗传的还是时差等外部干扰--都会促进糖尿病、免疫缺陷或癌症等疾病的发展。在分子水平上，生物钟基于细胞自主的时钟基因/蛋白质的转录反馈回路。在哺乳动物中，昼夜节律是以分层系统组织的，中央起搏器位于下丘脑视交叉上核（SCN）中，它接收来自视网膜的外部光信息，并在一个称为诱导的过程中重置其他大脑区域和整个身体的外围时钟。虽然在细胞和组织水平上昼夜节律计时的分子基础和生理输出已经被广泛研究，但对身体不同时钟之间的通信知之甚少。虽然尚未发现一般的时钟重置信号，但体液和神经元信号似乎都参与其中。本课题组和其他研究表明肾上腺和节律性分泌的、肾上腺皮质钟调节的糖皮质激素可能在这一过程中发挥重要作用，本课题将使用不同的转基因小鼠模型研究肾上腺钟的夹带、其在身体其他昼夜节律振荡器同步中的功能以及其在行为节律调节中的作用。我们的研究结果将有助于开发新的治疗方法，用于治疗因昼夜节律紊乱而导致的疾病，例如时差或轮班工作。