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...     

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。     

The chondrocyte-intrinsic circadian clock is disrupted in human osteoarthritis

Peripheral clocks are essential for driving cell differentiation. In osteoarthritis, loss of the normal differentiated chondrocyte (cartilage cell) phenotype is causative of disease. We investigated whether clock gene expression differed in osteoarthritic compared to “healthy” chondrocytes and used RNAi to determine whether the differences observed could affect chondrocyte phenotype. Following serum shock, PER2 expression was significantly higher, whereas BMAL1 expression was significantly lower, in osteoarthritic chondrocytes. Knockdown of BMAL1 in “healthy” chondrocytes was associated with higher cell proliferation and MMP13 expression, features characteristic of the osteoarthritic chondrocyte phenotype. Chondrocyte-intrinsic clock disruption may be a critical early step in osteoarthritis development.     

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.     

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。     

Waterborne copper disrupts circadian rhythm in red seabream (Pagrus major)

We investigated the effect of copper (Cu) on circadian rhythms in red seabream, Pagrus major, under various concentrations of Cu (10, 20, 30 and 40 μg/L). To examine variability in circadian rhythms, we measured changes in the period 2 (Per2), cryptochrome 1 (Cry1), serotonin and arylalkylamine N-acetyltransferase (AANAT2) proteins. We found that circadian rhythm-related plasma proteins were significantly lower in a high-Cu environment (30–40 μg/L) than in low-Cu concentration (0, 10, or 20 μg/L). Our results indicate that environmental Cu at concentrations greater than 30 μg/L can have deleterious effects on fish circadian rhythms.     

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.     

Light at night,clocks and health: from humans to wild organisms

The increasing use of electric lights has modified the natural light environment dramatically, posing novel challenges to both humans and wildlife. Indeed, several biomedical studies have linked artificial light at night to the disruption of circadian rhythms, with important consequences for human health, such as the increasing occurrence of metabolic syndromes, cancer and reduced immunity. In wild animals, light pollution is associated with changes in circadian behaviour, reproduction and predator–prey interactions, but we know little about the underlying physiological mechanisms and whether wild species suffer the same health problems as humans. In order to fill this gap, we advocate the need for integrating ecological studies in the field, with chronobiological approaches to identify and characterize pathways that may link temporal disruption caused by light at night and potential health and fitness consequences.     

Truck Drivers Sleep-Wake Time Arrangements

Irregular working hours, including night work, change sleep-wake time arrangements which in turn might affect the ability to drive safely. This study aims to compare the effects of an irregular and a fixed day shift system on the sleep-wake cycle of truck drivers. The investigation of sleep-wake cycle was carried-out with 37 truck drivers working on two transportation plants: 24 working on irregular working hours and 13 on fixed day shift. The truck drivers filled out sleep logs and wore actigraphs for 10 consecutive days to identify activity and rest episodes. The group working in irregular hours showed more sleep episodes per 24 h and they were shorter compared to the fixed shift group (p < 0.05). No differences were found between the two transportation plants. These results suggest an the influence of working hours on specific sleep-wake patterns. The polyphasic sleep pattern shown by irregular shift group could be a strategy to cope with sleep deprivation, which may account for their difficulty to resist falling asleep behind the wheel.     

The circadian locomotor rhythm of Hemideina thoracica (Orthoptera; Stenopelmatidae): the circadian clock as a population of interacting oscillators

ABSTRACT. The behaviour of the circadian locomotor rhythm of the New Zealand weta, Hemideina thoracica (White), supports the model that the underlying pacemaker consists of a population of weakly coupled oscillators. Certain patterns of locomotor activity, previously demonstrated almost exclusively in vertebrates, are presented here as evidence for the above hypothesis. They include after-effects of various pre-treatments, rhythm-splitting and spontaneous changes in the rhythm. After-effects, which describe the unstable behaviour of free-running circadian rhythms following particular experimental perturbations, have been observed in Hemideina following single light pulses, constant dim light, and laboratory and natural entrainment. Period changes occurred in the activity rhythm after single light pulses of 8-h and 12-h duration (25 lx). Constant dim light (0.1 lx) increased the free-running period (τ) of the activity rhythm, but the after-effect of constant dim light was either an increase or a decrease in τ. After-effects upon both τ and the active phase length of the activity rhythm were found following non-24-h light entrainment cycles with 8-h and 12-h light phases of 25 lx. Qualitative measurements of these after-effects upon τ are presented which reveal a relationship between both the direction and amount of change in τ, and the difference between entrainment cycle length (T) and pre-entrainment free-running period. The after-effect of natural entrainment was an initial short-period free-run (τ < 24h) lasting 5–10 days, generally followed by a rapid period lengthening to τ= 25–26 h. Support for the population model was provided by spontaneous dampening, recovery, and period changes of the rhythm, together with the disruption of the active phase following critical light perturbations, and rhythm-splitting. These Hemideina results are compared with the simulations of the Coupled Stochastic System of Enright (1980).