Finding time for dinner: neural and molecular mechanisms of food-entrainable circadian clocks

找到吃晚饭的时间：食物生物钟的神经和分子机制

• 批准号: 155172-2009
• 负责人: Mistlberger, Ralph
• 金额: $ 4.08万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=451996
• 关键词: Finding; time; dinner; neural; molecular

The behaviour and physiology of mammals is regulated by endogenous circadian (24 h) clocks in the brain and in peripheral organs and tissues. These clocks generate daily rhythms of sleep-wake, appetite and body temperature and coordinate the functions of all organ systems with daily cycles of light-dark and mealtimes. A master circadian clock located in the hypothalamus is critical for synchronizing daily rhythms to light-dark cycles, but synchrony to mealtimes is mediated by one or more other circadian clocks at an unknown location. Our research aims to understand the brain mechanisms by which food regulates daily rhythms. Recent advances in the molecular biology of circadian timekeeping have identified a number of genes that exhibit circadian rhythms of expression, and that form interlocking feedback loops that produce self-sustaining, cell autonomous rhythmicity. We will use immunocytochemical and photometric techniques to measure clock genes and identify brain regions that oscillate in synchrony with one or two daily mealtimes. We will explore the role of specific rhythmic brain regions in the control of meal synchronized rhythms, using lesion techniques. We will explore the role of specific clock genes for meal synchronized rhythms using clock gene mutant mice. Finally, we will characterize the effects of meal timing and food deprivation on the rate at which behavioural and physiological rhythms re-synchronize following phase shifts of the light-dark cycle, simulating east or west travel or shift work rotations. The results of these studies will clarify neural and molecular mechanisms by which food regulates daily rhythms and may suggest techniques for minimizing disruption of circadian rhythms following travel or shift rotation.

哺乳动物的行为和生理机能受到大脑以及周围器官和组织内源性昼夜节律（24 小时）时钟的调节。这些时钟产生每日的睡眠-觉醒、食欲和体温节律，并通过每日的明暗和进餐时间周期来协调所有器官系统的功能。位于下丘脑的主生物钟对于将每日节律与明暗周期同步至关重要，但进餐时间的同步是由未知位置的一个或多个其他生物钟介导的。我们的研究旨在了解食物调节日常节律的大脑机制。昼夜节律计时分子生物学的最新进展已经鉴定出许多表现出昼夜节律表达节律的基因，并形成连锁反馈环路，从而产生自我维持的细胞自主节律性。我们将使用免疫细胞化学和光度测量技术来测量时钟基因并识别与每天一两次进餐时间同步振荡的大脑区域。我们将使用损伤技术探索特定节律性大脑区域在控制进餐同步节律中的作用。我们将使用时钟基因突变小鼠探索特定时钟基因对膳食同步节律的作用。最后，我们将描述进餐时间和食物匮乏对行为和生理节律在明暗周期相移后重新同步的速率的影响，模拟向东或向西旅行或轮班工作轮换。这些研究的结果将阐明食物调节日常节律的神经和分子机制，并可能提出尽量减少旅行或轮班后昼夜节律破坏的技术。