运动介导的心脏代谢与生物钟相互调节作用研究

在哺乳动物中,昼夜节律主要由生物钟基因的转录翻译反馈回路产生,生物钟基因通过转录翻译反馈回路调控下游的时钟控制基因,从而影响体内的各种生理活动。心脏作为人体外周组织中的重要器官,其生物钟系统受到运动和营养等授时因子的调控。当心肌细胞的生物钟基因被遗传性破坏或表达异常时,会严重影响心脏的代谢活动,导致心脏生理功能减退,增加心脏不良事件的发生风险,因此心脏生物钟在维持心脏代谢活动和生理功能方面发挥着重要作用。运动作为授时因子,可以独立于中枢生物钟对心脏生物钟进行调节。同时运动作为改善心血管功能的重要手段,可能通过激活下丘脑-垂体-肾上腺轴（HPA）和交感-肾上腺-髓质轴（SAM）、调节能量代谢等途径影响心脏的代谢活动和生物钟基因的转录,维持心脏生物钟的稳定,促进心脏健康。对运动调控心脏生物钟的机制研究,可以为倒班、熬夜人群以及心血管疾病患者提供新的预防和治疗思路。未来需要更多研究来探索运动调节心脏代谢活动和生物钟的机制、运动对光周期诱导的昼夜节律紊乱心脏生物钟的影响及机制以及运动调节心脏生物钟对其他外周器官代谢活动和昼夜节律的影响。     

生物钟机制研究进展

由生物体内源性生物钟所产生的昼夜节律是近年来生命科学的研究热点之一。几种模型生物（蓝细菌、脉孢菌、拟南芥、果蝇、小鼠）的生物钟相关基因相继被克隆和鉴定,为理解昼夜节律的分子机制奠定了基础。振荡器蛋白对其编码基因的负反馈调控可能是不同生物的生物运作普遍机制,在此基础上,不同生物有不尽相同的调控方式;隐色素可能是高等生物的共同生物钟光受体。     

Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans

This study investigated the impact of sleep deprivation on the human circadian system. Plasma melatonin and cortisol levels and leukocyte expression levels of 12 genes were examined over 48?h (sleep vs. no-sleep nights) in 12 young males (mean?±?SD: 23?±?5 yrs). During one night of total sleep deprivation, BMAL1 expression was suppressed, the heat shock gene HSPA1B expression was induced, and the amplitude of the melatonin rhythm increased, whereas other high-amplitude clock gene rhythms (e.g., PER1-3, REV-ERBα) remained unaffected. These data suggest that the core clock mechanism in peripheral oscillators is compromised during acute sleep deprivation.     

Life's 24-hour clock: molecular control of circadian rhythms in animal cells

Our sleep–wake cycles and many other 24-hour rhythms of behavior and physiology persist in the absence of environmental cues. Genetic and biochemical studies have shown that such rhythms are controlled by internal molecular clocks. These are assembled from the cycling RNA and protein products of a small group of genes that are conserved throughout the animal kingdom.     

Association between circadian genes,bipolar disorders and chronotypes

Abnormalities in circadian rhythms play an important role in the pathogenesis of bipolar disorders (BD). Previous genetic studies have reported discrepant results regarding associations between circadian genes and susceptibility to BD. Furthermore, plausible behavioral consequences of at-risk variants remain unclear since there is a paucity of correlates with phenotypic biomarkers such as chronotypes. Here, we combined association studies with a genotype/phenotype correlation in order to determine which circadian genes variants may be associated with the circadian phenotypes observed in patients with BD. First, we compared the allele frequencies of 353 single nucleotide polymorphisms spanning 21 circadian genes in two independent samples of patients with BD and controls. The meta-analysis combining both samples showed a significant association between rs774045 in TIMELESS (OR?=?1.49 95%CI[1.18–1.88]; p?=?0.0008) and rs782931 in RORA (OR?=?1.31 95%CI[1.12–1.54]; p?=?0.0006) and BD. Then we used a “reverse phenotyping approach” to look for association between these two polymorphisms and circadian phenotypes in a subsample of patients and controls. We found that rs774045 was associated with eveningness (p?=?0.04) and languid circadian type (p?=?0.01), whereas rs782931 was associated with rigid circadian type (p?=?0.01). Altogether, these findings suggest that these variants in the TIMELESS and RORA genes may confer susceptibility to BD and impact on circadian phenotypes in carriers who thus had lower ability to properly adapt to external cues.     

Serotonergic potentiation of dark pulse-induced phase-shifting effects at midday in hamsters

In mammals, resetting of the suprachiasmatic clock (SCN) by behavioral activation or serotonin (5-HT) agonists is mimicked by dark pulses, presented during subjective day in constant light (LL). Because behavioral resetting may be mediated in part by 5-HT inputs to the SCN, here we determined whether 5-HT system can modulate dark-induced phase-shifts in Syrian hamsters housed in LL. Two hours of darkness at mid-subjective day (circadian time 6; CT-6) resulted in increased concentrations of 5-HT in the SCN tissue and induction of c-FOS expression in the raphe nuclei. Injections of the 5-HT_1A/7 agonist (+)8-OH-DPAT or dark pulses at CT-6 induced phase-advances of the wheel-running activity rhythm and down-regulated the expression of the clock genes Per1-2 and c-FOS in the SCN in a similar way. The combination of both treatments [(+)8-OH-DPAT + dark pulses], however, resulted in larger phase-advances, while associated molecular changes were not significantly modified, except for the gene Dbp , in comparison to (+)8-OH-DPAT or dark pulses alone. Dark resetting was blocked by pre-treatment with a 5-HT₇ antagonist, but not with a 5-HT_1A antagonist. The additive phase-shifts of two different cues to reset the SCN clock open wide the gateway for non-photic shifting, leading to new strategies in chronotherapy.     

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...     

Egg-laying rhythm in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Extensive research has been carried out to understand how circadian clocks regulate various physiological processes in organisms. The discovery of clock genes and the molecular clockwork has helped researchers to understand the possible role of these genes in regulating various metabolic processes. In Drosophila melanogaster, many studies have shown that the basic architecture of circadian clocks is multi-oscillatory. In nature, different neuronal subgroups in the brain of D. melanogaster have been demonstrated to control different circadian behavioural rhythms or different aspects of the same circadian rhythm. Among the circadian phenomena that have been studied so far in Drosophila, the egg-laying rhythm is unique, and relatively less explored. Unlike most other circadian rhythms, the egg-laying rhythm is rhythmic under constant light conditions, and the endogenous or free-running period of the rhythm is greater than those of most other rhythms. Although the clock genes and neurons required for the persistence of adult emergence and activity/rest rhythms have been studied extensively, those underlying the circadian egg-laying rhythm still remain largely unknown. In this review, we discuss our current understanding of the circadian egg-laying rhythm in D. melanogaster, and the possible molecular and physiological mechanisms that control the rhythmic output of the egg-laying process.     

Changes in circadian parameters of humbug damselfish,Dascyllus aruanus according to lunar phase shifts in Micronesia

The objectives of this study were to test the nighttime effects of the lunar phase on circadian rhythm in the humbug damselfish, Dascyllus aruanus. We measured moonlight intensities at eight different phases across the lunar cycle. At each lunar phase, the circadian rhythm was evaluated by measuring the clock genes cryptochrome 1 and period 2. In addition, we measured arylalkylamine N-acetyltransferase 2 (AANAT2), melatonin and melatonin receptor 1 (MT-R1). The moonlight intensity was highest at full moon and lowest during the waning crescent. Clock gene expression was highest during the full moon compared to the other phases. By contrast, the plasma concentrations of AANAT2 and melatonin and the MT-R1 mRNA expression were highest during the full moon phase. Our results suggest that moonlight affects circadian rhythm patterns in the humbug damselfish. There is a need to investigate potential other physiological effects of lunar phase shifts.     

蓝藻生物钟分子机理的研究进展

蓝藻是具有内源性生物钟的简单生物.虽然蓝藻生物钟具有跟真核生物同样的基础特征,但其相关基因和蛋白质与真核生物没有同源性.蓝藻生物钟的核心是kai基因簇及其编码的蛋白KaiA,KaiB和KaiC.这三种Kai蛋白相互作用调节KaiC的磷酸化状态,从而产生昼夜节律信息.KaiC的磷酸化循环是昼夜节律的起博器,调控包括kai基因在内的相关基因的节律性表达.组氨酸蛋白激酶的磷酸化传递可将环境信息输入和将节律信息输出生物钟核心.     

Dexamethasone induces high-amplitude rhythms in preadipocytes,But hinders circadian expression in differentiated adipocytes

Glucocorticoids induce circadian gene expression in cultured cells and change the phase of circadian gene expression in vivo. In addition, glucocorticoids induce differentiation of preadipocyte to adipocytes. We set out to test the effect of dexamethasone, a glucocorticoid receptor agonist, on circadian rhythms in 3T3-L1 differentiated adipocytes. Our results show that differentiated adipocytes exhibit robust circadian rhythms without dexamethasone. Dexamethasone induces phase changes and increases the amplitude of circadian gene expression in nondifferentiated 3T3-L1 preadipocytes. However, dexamethasone had an opposite effect on differentiated adipocytes, leading to low-amplitude circadian expression. In conclusion, although glucocorticoids reset circadian rhythms, once rhythms are reset, glucocorticoid administration hinders circadian expression.