动物内源褪黑素调控生物节律的研究进展

内源褪黑素对人类和其他哺乳动物的节律行为具有调控功能。生物节律是自然进化赋予生命的基本特征之一,生物体的生命活动受到生物节律的控制与影响。在哺乳动物中,节律调控中心是松果体,其主要功能是合成和分泌褪黑素。褪黑素广泛参与生物体节律行为的调节,本文从褪黑素的产生和作用机制,分别阐述褪黑素对昼夜节律行为和多种年节律行为的调控作用,同时明确褪黑素与生物钟及神经内分泌系统的直接作用和反馈互动的复杂集合,进一步揭示褪黑素调控生物节律的重要作用,以期为褪黑素的基础研究以及未来探究生物体的生物钟内源性发生机制提供参考。     

Circadian clocks in the mammalian brain

Daily cycles in physiology and behaviour are probably a universal feature of multicellular organisms. These rhythms are predominantly driven by endogenous clocks with a periodicity approximating to one day, i.e. circadian. In mammals, the circadian clock governing activity/ rest, neuroendocrine and autonomic rhythms lies in the hypothalamus, in the suprachiasmatic nuclei (SCN). Intrinsic circadian oscillators are also present in the retina. The SCN "clockwork" is based on a cell autonomous, genetically determined mechanism. Mammalian homologues of a number of Drosophila genes which encode elements of the fly circadian mechanism have recently been identified. In Drosophila, the protein products of these genes interact in a negative feedback loop, establishing a circadian cycle in gene expression. Characterisation of the roles played by putative mammalian clock genes in the SCN, and how the emergent cellular signal imposes order over the entire neuraxis, will provide a fundamental contribution to our understanding of the molecular basis of behaviour. BioEssays 22:23-31, 2000.     

哺乳动物昼夜节律生物钟研究进展

昼夜节律生物钟是一种以近似24小时为周期的自主维持的振荡器,在分子水平上,该振荡器是一个由9个基因组成的转录翻译反馈环路系统。它能受外界环境影响重新设置节律,使自身机体活动处于最佳状态。除了进行自我调节外,生物钟基因还能通过调节代谢途径中特定基因表达而影响机体生理生化过程。在过去的几年里,借用遗传学和分子生物学工具,我们对哺乳动物昼夜节律生物钟的分子基础有了新的认识,本文综述了这一进展,并展望了它们在研究人的昼夜节律行为异常领域的前景。     

生物钟在卵巢生理和病理中的作用

哺乳动物的昼夜节律是基因编码的分子钟在体内产生的一种以大约24 h为周期的生理现象,使机体的生理过程与外界环境的变化相协调,是对环境适应的一种表现.在哺乳动物中,繁殖生理功能受生物钟系统的调节.在下丘脑-垂体-卵巢(hypothalamic-pituitary-ovarian,HPO)轴的各组织中均已观察到生物钟基因的...     

Understanding circadian rhythmicity in Neurospora crassa: from behavior to genes and back again

Circadian clocks have been described in organisms ranging in complexity from unicells to mammals, in which they function to control daily rhythms in cellular activities and behavior. The significance of a detailed understanding of the clock can be appreciated by its ubiquity and its established involvement in human physiology, including endocrine function, sleep/wake cycles, psychiatric illness, and drug tolerances and effectiveness. Because the clock in all organisms is assembled within the cell and clock mechanisms are evolutionarily conserved, simple eukaryotes provide appropriate experimental systems for dissecting the clock. Significant progress has been made in deciphering the circadian system in Neurospora crassa using both genetic and molecular approaches, and Neurospora has contributed greatly to our understanding of (1) the feedback cycle that comprises a circadian oscillator, (2) the mechanisms by which the clock is kept in synchrony with the environment, and (3) the genes that reside in rhythmic output pathways. Importantly, the lessons learned in Neurospora are relevant to our understanding of clocks in higher eukaryotes.     

Crosstalk between xenobiotics metabolism and circadian clock

Many aspects of physiology and behavior in organisms from bacteria to man are subjected to circadian regulation. Indeed, the major function of the circadian clock consists in the adaptation of physiology to daily environmental change and the accompanying stresses such as exposition to UV-light and food-contained toxic compounds. In this way, most aspects of xenobiotic detoxification are subjected to circadian regulation. These phenomena are now considered as the molecular basis for the time-dependence of drug toxicities and efficacy. However, there is now evidences that these toxic compounds can, in turn, regulate circadian gene expression and thus influence circadian rhythms. As food seems to be the major regulator of peripheral clock, the possibility that food-contained toxic compounds participate in the entrainment of the clock will be discussed.     

How many pieces to build a circadian clock?

Biological rhythms represent a fundamental property of various living organisms. In particular, circadian rhythms, i.e. rhythms with a period close to 24 hours, help organisms to adapt to environmental daily rhythms. Although various factors can entrain or reset rhythms, they persist even in the absence of external timing cue, showing that their generation is endogenous. Indeed, the suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be the main circadian clock in mammals. Isolated SCN neurons have been shown to display circadian rhythms, and in each cell, a set of genes, called "clock genes", are devoted to the generation and regulation of rhythms. Recently, it has become obvious that the clock located in the SCN is not homogenous, but is rather composed of multiple functional components somewhat reminiscent of its neurochemical organization. The significance and implications of these findings are still poorly understood but pave the way for future exciting studies. Here, current knowledge concerning these distinct neuronal populations and the ways through which synchronization could be achieved, as well as the potential role of neuropeptides in both photic and non-photic resetting of the clock, are summarized. Finally, we discuss the role of the SCN within the circadian system, which also includes oscillators located in various tissues and cell types.     

Dexras1: shaping the responsiveness of the circadian clock

Living organisms are endowed with an autonomous timekeeping program that not only maintains circadian rhythms of behaviour and physiology but is reset by cues from the external, cyclic environment. Intracellular signaling events that mediate entrainment of the mammalian circadian clock by photic (light) as well as non-photic inputs are only beginning to be elucidated. Dexras1 is a novel Ras-like G protein that modulates multiple signaling cascades. Genetic ablation of Dexras1 in mice (dexras1(-/-)) results in altered responsiveness of the master circadian clock to photic and non-photic cues. This review will attempt to provide mechanistic insights into the involvement of Dexras1 in biological timing processes based on its role as a modulator of signal transduction.     

Cellular oscillators: rhythmic gene expression and metabolism

Many biological processes are driven by biological clocks that, depending on the frequency they generate, are classified into ultradian, circadian and infradian oscillators. In virtually all light-sensitive organisms from cyanobacteria to humans, a circadian timing system adapts cyclic physiology to geophysical time. Recent evidence suggests that even in mammals circadian oscillators function in a cell-autonomous manner. In yeast, an ultradian oscillator regulates cyclic respiratory activity and global gene expression. Circadian oscillators and the ultradian yeast respiratory clock share at least four properties: they follow limit-cycle kinetics, interweave with cellular metabolism, are temperature-compensated and influence the cell division clock.