生物钟基因与哺乳动物生殖

近日节律是生物节律中最重要的一种。它是一种以近似24 h为周期的自主振荡器,普遍存在于生物界中。近日节律主要受生物钟基因的调控,在哺乳动物中已发现时钟基因(Clock)、周期基因(Period,Per)家族、隐花色素基因(Cryptochrome1,Cry)家族、Bmal1(Brain and muscle ARNT-like 1)在内的多种重要的生物钟基因。这些基因及其蛋白质产物构成的反馈调节环是生物钟运行的分子基础。研究表明,生物钟基因不仅仅在近日节律的中枢系统中存在表达,在外周组织中也存在表达。而且生物钟基因与哺乳动物生殖密切相关,提示可能在生殖领域中具有重要的调控作用。主要从几个关键生物钟基因的发现、在近日节律和非近日节律中的调节作用、以及与哺乳动物生殖的关系做一综述。     

生物节律影响巨核细胞发育和血小板产生的研究进展

自然界中生物体的生命活动、生活习性都存在着一定的周期性变化。生物昼夜节律的产生是以内源性的生物钟系统为基础的。生物钟不仅易受到外界环境的影响,而且可以通过调控一系列特定的下游基因的表达,影响生物体的生理生化过程。巨核细胞是生成血小板的前体细胞,经过分化、增殖、成熟和裂解,最终生成血小板。血小板是一种没有细胞核的特殊细胞,在生理性止血和器官修复上发挥着重要作用,同时参与血栓等多种疾病的发生。近几年借助现代分子生物学和细胞生物学手段,证实了哺乳动物的巨核细胞和血小板的生成呈现明显的周期性的变化,利用生物钟基因缺失模型进一步发现了生物钟基因对巨核细胞和血小板的影响。本文概述了生物节律对巨核细胞和血小板的影响,为进一步研究巨核细胞的发育和血小板生成机制提供了参考。     

生物节律影响巨核细胞发育和血小板产生的研究进展

自然界中生物体的生命活动、生活习性都存在着一定的周期性变化。生物昼夜节律的产生是以内源性的生物钟系统为基础的。生物钟不仅易受到外界环境的影响,而且可以通过调控一系列特定的下游基因的表达,影响生物体的生理生化过程。巨核细胞是生成血小板的前体细胞,经过分化、增殖、成熟和裂解,最终生成血小板。血小板是一种没有细胞核的特殊细胞,在生理性止血和器官修复上发挥着重要作用,同时参与血栓等多种疾病的发生。近几年借助现代分子生物学和细胞生物学手段。证实了哺乳动物的巨核细胞和血小板的生成呈现明显的周期性的变化,利用生物钟基因缺失模型进一步发现了生物钟基因对巨核细胞和血小板的影响。本文概述了生物节律对巨核细胞和血小板的影响,为进一步研究巨核细胞的发育和血小板生成机制提供了参考。     

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。     

环境光对哺乳动物昼夜节律和大脑功能的影响

昼夜循环对人类和其他动物的生理和行为有着巨大的影响。光照条件能影响动物的视觉成像,并通过向大脑中的生物钟中心发送信号来调整生理和行为的节律。环境光向生物钟传递信号的系统包含了一个复杂的神经递质复合体-受体-第二信使系统。在夜间曝光能迅速启动下丘脑视交叉上核中大量相关的早期基因。此外,许多白天活动的物种,通常都是在光照条件下获得认知。本文综述了环境光对哺乳动物睡眠、生物节律、大脑认知能力和基因表达等生理和行为方面的影响。     

哺乳动物卵巢生物钟的研究进展

近年来,越来越多的研究发现生物钟系统在许多生理活动中,包括心血管、内分泌、免疫、生殖等系统的生理,都起着重要作用。随着2006年卵巢生物钟的发现,生殖系统生物钟成为新的研究热点。研究发现卵巢生物钟不仅影响排卵,而且还控制类固醇激素的释放。卵巢生物钟属外围生物钟,受到中央生物钟(SCN)神经内分泌信号的调控。还发现下丘脑-垂体-卵巢(HPG)轴上各水平都存在生物钟,HPG轴上各生物钟失同步影响生殖能力,这可能导致一些疾病发生的病因。本文总结近十年的关于卵巢生物钟的研究,列举哺乳动物卵巢生物钟存在的证据,并阐述生物钟在雌鼠正常生殖生理过程,及在生殖系统疾病病理过程中的作用及其分子机制。     

生物钟与肠道菌群调控哺乳动物能量代谢研究进展

生物钟作为哺乳动物进化过程中产生的一种适应机体内外环境昼夜变化的内在机制,控制着机体的睡眠-觉醒及进食等生理活动,使生物体在每个昼夜周期的能量需求和营养供给呈现出与环境相适应的节律性变化。哺乳动物的肝脏、骨骼肌、胰腺、心血管等组织的葡萄糖代谢、脂质代谢和激素分泌等都受到生物钟的调控。作为宿主特殊的“器官”,肠道菌群在共同进化过程中与宿主微环境(组织、细胞、代谢产物)构成了一个微生态系统,在宿主对营养物质的消化和吸收过程中发挥重要作用。近年来的一些研究证据表明,肠道菌群的构成、数量、定植以及功能活动均具有显著的昼夜节律性变化,而这与生物钟调控下的各种生理功能变化是密切相关的。此外,有研究发现肠道菌群可通过分解宿主无法消化的膳食纤维等营养物质产生短链脂肪酸等代谢产物,部分代谢产物具有调节宿主生物钟并影响代谢的功能。本文将重点阐述生物钟与肠道菌群的互作及其对哺乳动物能量代谢的影响,以期为代谢性疾病的预防和治疗提供新的线索和思路。     

Bmal1基因与衰老的关系

Bmall（brain and muscle ARNT-like-1）基因是哺乳动物生物钟转录、翻译反馈环中的核心成分,以异源二聚体的形式在反馈环中发挥重要的正调节作用.该基因的发现使得生物钟的基因分子调控机制有了突破性进展;研究过程中发现,Bmal1基因可能同我们的衰老也有直接的联系.     

视网膜生物钟研究进展

昼夜节律生物钟是以24h为周期的自主维持的振荡器。在高等的多细胞生物中,生物钟可以分为母钟和子钟。研究表明哺乳动物的母钟位于下丘脑视交叉上核(suprachiasmatic nucleus,SCN),由此发出信息控制全身的节律活动;子钟位于组织细胞内,调控效应器的节律。在分子水平上,生物钟的振荡由自身调控反馈环路的转录和翻译组成,并接受外界环境因素的影响,通过下丘脑视叉上核(Suprachiasmatic Nucleus,SCN)中枢震荡器的同步整和而产生作用。视网膜是一种十分节律性的组织,许多生化的、细胞的和生理的过程都是以节律的方式来进行的,如视觉灵敏度、视网膜杆细胞外片层脱落和视网膜色素上皮细胞的吞噬作用、光受体中的视觉色素基因的快速表达等。生物钟存在于很多脊椎动物的视网膜中,被认为是一种外周生物钟。本文综述了视网膜生物钟,生物钟信号传输以及生物钟网络等的最新研究进展。     

The protective effect of cycloastragenol on aging mouse circadian rhythmic disorder induced by d-galactose

Aging process in mammals is associated with a decline in amplitude and a long period of circadian behaviors which are regulated by a central circadian regulator in the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. It is unclear whether enhancing clock function can retard aging. Using fibroblasts expressing per2::lucSV and senescent cells, we revealed cycloastragenol (CAG), a natural aglycone derivative from astragaloside IV, as a clock amplitude enhancing small molecule. CAG could activate telomerase to antiaging, but no reports focused on its effects on circadian rhythm disorders in aging mice. Here we analyze the potential effects of CAG on d -galactose-induced aging mice on the circadian behavior and expression of clock genes. For this purpose, CAG (20 mg/kg orally), was administered daily to d -galactose (150 mg/kg, subcutaneous) mice model of aging for 6 weeks. An actogram analysis of free-running activity of these mice showed that CAG significantly enhances the locomotor activity. We further found that CAG increase expressions of per2 and bmal1 genes in liver and kidney of aging mouse. Furthermore, CAG enhanced clock protein BMAL1 and PER2 levels in aging mouse liver and SCN. Our results indicated that the CAG could restore the behavior of circadian rhythm in aging mice induced by d -galactose. These data of present study suggested that CAG could be used as a novel therapeutic strategy for the treatment of age-related circadian rhythm disruption.     

Circadian rhythms of indoleamines and serotonin N-acetyltransferase activity in the pineal gland

Conclusion The circadian rhythm of melatonin synthesis in the pineal glands of various species has been summarized. The night-time elevation of melatonin content is in most if not all cases regulated by the change of N-acetyltransferase activity. In mammals, the N-acetyltransferase rhythm is controlled by the central nervous system, presumably by suprachiasmatic nuclei in hypothalamus through the superior cervical ganglion. In birds, the circadian oscillator that regulates the N-acetyltransferase rhythm is located in the pineal glands. The avian pineal gland may play a biological clock function to control the circadian rhythms in physiological, endocrinological and biochemical processes via pineal hormone melatonin.     

A randomized,double-blind and placebo-controlled crossover trial on the effect of l-ornithine ingestion on the human circadian clock

ABSTRACT

In mammals, daily physiological events are regulated by the circadian rhythm, which comprises two types of internal clocks: the central clock and peripheral clocks. Circadian rhythm plays an important role in maintaining physiological functions including the sleep-wake cycle, body temperature, metabolism and organ functions. Circadian rhythm disorder, which is caused, for example, by an irregular lifestyle or long-haul travel, increases the risk of developing disease; therefore, it is important to properly maintain the rhythm of the circadian clock. Food and the circadian clock system are known to be closely linked. Studies on rodents suggest that ingesting specific food ingredients, such as the flavonoid nobiletin, fish oil, the polyphenol resveratrol and the amino acid L-ornithine affects the circadian clock. However, there are few reports on the foods that affect these circadian clocks in humans. In this study, therefore, we examined whether L-ornithine affects the human central clock in a crossover design placebo-controlled human trial. In total, 28 healthy adults (i.e. ≥20 years) were randomly divided into two groups and completed the study protocol. In the 1st intake period, participants were asked to take either L-ornithine (400 mg) capsules or placebo capsules for 7 days. After 7 days’ interval, they then took the alternative test capsules for 7 days in the 2nd intake period. On the final day of each intake period, saliva was sampled at various time points in the dim light condition, and the concentration of melatonin was quantified to evaluate the phase of the central clock. The results revealed that dim light melatonin onset, a recognized marker of central circadian phase, was delayed by 15 min after ingestion of L-ornithine. Not only is this finding an indication that L-ornithine affects the human central clock, but it also demonstrates that the human central clock can be regulated by food ingredients.