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Barclay, J. L., Husse, J., Bode, B., Naujokat, N., Meyer-Kovac, J., Schmid, S. M., et al. (2012). Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork. PLoS One, 7(5), e37150.
Abstract: Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers.
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Bullough, J. D., Rea, M. S., & Figueiro, M. G. (2006). Of mice and women: light as a circadian stimulus in breast cancer research. Cancer Causes Control, 17(4), 375–383.
Abstract: OBJECTIVE: Nocturnal rodents are frequently used as models in human breast cancer research, but these species have very different visual and circadian systems and, therefore, very different responses to optical radiation or, informally, light. Because of the impact of light on the circadian system and because recent evidence suggests that cancer risk might be related to circadian disruption, it is becoming increasingly clear that optical radiation must be properly characterized for both nocturnal rodents and diurnal humans to make significant progress in unraveling links between circadian disruption and breast cancer. In this paper, we propose a quantitative framework for comparing radiometric and photometric quantities in human and rodent studies. METHODS: We reviewed published research on light as a circadian stimulus for humans and rodents. Both suppression of nocturnal melatonin and phase shifting were examined as outcome measures for the circadian system. RESULTS: The data were used to develop quantitative comparisons regarding the absolute and spectral sensitivity for the circadian systems of humans and nocturnal rodents. CONCLUSIONS: Two models of circadian phototransduction, for mouse and humans, have been published providing spectral sensitivities for these two species. Despite some methodological variations among the studies reviewed, the circadian systems of nocturnal rodents are approximately 10,000 times more sensitive to optical radiation than that of humans. Circadian effectiveness of different sources for both humans and nocturnal rodents are offered together with a scale relating their absolute sensitivities. Instruments calibrated in terms of conventional photometric units (e.g., lux) will not accurately characterize the circadian stimulus for either humans or rodents.
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Chaves, I., Pokorny, R., Byrdin, M., Hoang, N., Ritz, T., Brettel, K., et al. (2011). The cryptochromes: blue light photoreceptors in plants and animals. Annu Rev Plant Biol, 62, 335–364.
Abstract: Cryptochromes are flavoprotein photoreceptors first identified in Arabidopsis thaliana, where they play key roles in growth and development. Subsequently identified in prokaryotes, archaea, and many eukaryotes, cryptochromes function in the animal circadian clock and are proposed as magnetoreceptors in migratory birds. Cryptochromes are closely structurally related to photolyases, evolutionarily ancient flavoproteins that catalyze light-dependent DNA repair. Here, we review the structural, photochemical, and molecular properties of cry-DASH, plant, and animal cryptochromes in relation to biological signaling mechanisms and uncover common features that may contribute to better understanding the function of cryptochromes in diverse systems including in man.
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Evans, J. A., Elliott, J. A., & Gorman, M. R. (2009). Dim nighttime illumination accelerates adjustment to timezone travel in an animal model. Curr Biol, 19(4), R156–7.
Abstract: Jetlag reflects a mismatch between local and circadian time following rapid timezone travel [1]. Appropriately timed bright light can shift human circadian rhythms but recovery is slow (e.g., 1-2 days per timezone). Most symptoms subside after resynchronization, but chronic jetlag may have enduring negative effects [2], including even accelerated mortality in mice [3]. Melatonin, prescription drugs, and/or exercise may help shift the clock but, like bright light, require complex schedules of application [1]. Thus, there is a need for more efficient and practical treatments for addressing jetlag. In contrast to bright daytime lighting, nighttime conditions have received scant attention. By incorporating more naturalistic nighttime lighting comparable in intensity to dim moonlight, we demonstrate that recovery after simulated jetlag is accelerated when nights are dimly lit rather than completely dark.
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Filipski, E., Li, X. M., & Levi, F. (2006). Disruption of circadian coordination and malignant growth. Cancer Causes Control, 17(4), 509–514.
Abstract: Altered circadian rhythms predicted for poor survival in patients with metastatic colorectal or breast cancer. An increased incidence of cancers has been reported in flying attendants and in women working predominantly at night. To explore the contribution of circadian structure to tumor growth we ablated the 24-h rest-activity cycle and markedly altered the rhythms in body temperature, serum corticosterone and lymphocyte count in mice by complete stereotaxic destruction of the suprachiasmatic nuclei (SCN) or by subjecting the mice to experimental chronic jet-lag. Such disruption of circadian coordination significantly accelerated malignant growth in two transplantable tumor models, Glasgow osteosarcoma and Pancreatic adenocarcinoma. The mRNA expression of clock genes per2 and reverb-alpha in controls displayed significant circadian rhythms in the liver (Cosinor, p=0.006 and p=0.003, respectively) and in the tumor (p=0.04 and p<0.001, respectively). Both rhythms were suppressed in the liver and in the tumor of jet lagged mice. This functional disturbance of molecular clock resulted in down regulation of p53 and overexpression of c-Myc, two effects which may favor cancer growth. CONCLUSIONS: These results indicate that circadian system could play an important role in malignant growth control. This should be taken into consideration in cancer prevention and therapy.
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