School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
Institute of Neurobiology, University of Lübeck, Lübeck, Germany.
Endocr Rev. 2019 Feb 1;40(1):66-95. doi: 10.1210/er.2018-00049.
A plethora of physiological processes show stable and synchronized daily oscillations that are either driven or modulated by biological clocks. A circadian pacemaker located in the suprachiasmatic nucleus of the ventral hypothalamus coordinates 24-hour oscillations of central and peripheral physiology with the environment. The circadian clockwork involved in driving rhythmic physiology is composed of various clock genes that are interlocked via a complex feedback loop to generate precise yet plastic oscillations of ∼24 hours. This review focuses on the specific role of the core clockwork gene Period1 and its paralogs on intra-oscillator and extra-oscillator functions, including, but not limited to, hippocampus-dependent processes, cardiovascular function, appetite control, as well as glucose and lipid homeostasis. Alterations in Period gene function have been implicated in a wide range of physical and mental disorders. At the same time, a variety of conditions including metabolic disorders also impact clock gene expression, resulting in circadian disruptions, which in turn often exacerbates the disease state.
大量的生理过程表现出稳定且同步的日周期振荡，这些振荡要么由生物钟驱动，要么受其调节。位于下丘脑腹侧视交叉上核的生物钟协调中枢和外周生理学的 24 小时振荡与环境的同步。驱动节律性生理的生物钟机制由各种时钟基因组成，这些基因通过复杂的反馈环相互锁定，产生精确但具有可塑性的约 24 小时振荡。本综述重点介绍核心生物钟基因 Period1 及其同源基因在振荡器内和振荡器外功能中的特定作用，包括但不限于海马依赖过程、心血管功能、食欲控制以及葡萄糖和脂质稳态。Period 基因功能的改变与广泛的身心障碍有关。同时，包括代谢紊乱在内的多种情况也会影响时钟基因的表达，导致生物钟紊乱，进而常常使疾病恶化。
