|
|
Cajochen, C., Jud, C., Munch, M., Kobialka, S., Wirz-Justice, A., & Albrecht, U. (2006). Evening exposure to blue light stimulates the expression of the clock gene PER2 in humans. Eur J Neurosci, 23(4), 1082–1086.
Abstract: We developed a non-invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion. We also have the first evidence that induction of human PER2 expression is stimulated by exposing subjects to 2 h of light in the evening. This increase in PER2 expression was statistically significant in comparison to a non-light control condition only after light at 460 nm (blue) but not after light exposure at 550 nm (green). Our results indicate that the non-image-forming visual system is involved in human circadian gene expression. The demonstration of a functional circadian machinery in human buccal samples and its response to light opens the door for investigation of human circadian rhythms at the gene level and their associated disorders.
|
|
|
|
Chellappa, S. L., Viola, A. U., Schmidt, C., Bachmann, V., Gabel, V., Maire, M., et al. (2012). Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3. J Clin Endocrinol Metab, 97(3), E433–7.
Abstract: CONTEXT: Light exposure, particularly at the short-wavelength range, triggers several nonvisual responses in humans. However, the extent to which the melatonin-suppressing and alerting effect of light differs among individuals remains unknown. OBJECTIVE: Here we investigated whether blue-enriched polychromatic light impacts differentially on melatonin and subjective and objective alertness in healthy participants genotyped for the PERIOD3 (PER3) variable-number, tandem-repeat polymorphism. DESIGN, SETTING, AND PARTICIPANTS: Eighteen healthy young men homozygous for the PER3 polymorphism (PER3(5/5)and PER3(4/4)) underwent a balanced crossover design during the winter season, with light exposure to compact fluorescent lamps of 40 lux at 6500 K and at 2500 K during 2 h in the evening. RESULTS: In comparison to light at 2500 K, blue-enriched light at 6500 K induced a significant suppression of the evening rise in endogenous melatonin levels in PER3(5/5) individuals but not in PER3(4/4). Likewise, PER3(5/5) individuals exhibited a more pronounced alerting response to light at 6500 K than PER3(4/4) volunteers. Waking electroencephalographic activity in the theta range (5-7 Hz), a putative correlate of sleepiness, was drastically attenuated during light exposure at 6500 K in PER3(5/5) individuals as compared with PER3(4/4). CONCLUSIONS: We provide first evidence that humans homozygous for the PER3 5/5 allele are particularly sensitive to blue-enriched light, as indexed by the suppression of endogenous melatonin and waking theta activity. Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in the sleep-wake regulation.
|
|
|
|
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.
|
|
|
|
Froy, O., Gotter, A. L., Casselman, A. L., & Reppert, S. M. (2003). Illuminating the circadian clock in monarch butterfly migration. Science, 300(5623), 1303–1305.
Abstract: Migratory monarch butterflies use a time-compensated Sun compass to navigate to their overwintering grounds in Mexico. Here, we report that constant light, which disrupts circadian clock function at both the behavioral and molecular levels in monarchs, also disrupts the time-compensated component of flight navigation. We further show that ultraviolet light is important for flight navigation but is not required for photic entrainment of circadian rhythms. Tracing these distinct light-input pathways into the brain should aid our understanding of the clock-compass mechanisms necessary for successful migration.
|
|
|
|
Kempinger, L., Dittmann, R., Rieger, D., & Helfrich-Forster, C. (2009). The nocturnal activity of fruit flies exposed to artificial moonlight is partly caused by direct light effects on the activity level that bypass the endogenous clock. Chronobiol Int, 26(2), 151–166.
Abstract: Artificial moonlight was recently shown to shift the endogenous clock of fruit flies and make them nocturnal. To test whether this nocturnal activity is partly due to masking effects of light, we exposed the clock-mutants per(01), tim(01), per(01);tim(01), cyc(01), and Clk(JRK) to light/dark and light/dim-light cycles and determined the activity level during the day and night. We found that under moonlit nights, all clock mutants shifted their activity significantly into the night, suggesting that this effect is independent of the clock. We also recorded the flies under continuous artificial moonlight and darkness to judge the effect of dim constant light on the activity level. All mutants, except Clk(JRK) flies, were significantly more active under artificial moonlight conditions than under complete darkness. Unexpectedly, we found residual rhythmicity of per(01) and especially tim(01) mutants under these conditions, suggesting that TIM and especially PER retained some activity in the absence of its respective partner. Nevertheless, as even the double mutants and the cyc(01) and Clk(JRK) mutants shifted their activity into the night, we conclude that dim light stimulates the activity of fruit flies in a clock-independent manner. Thus, nocturnal light has a twofold influence on flies: it shifts the circadian clock, and it increases nocturnal activity independently of the clock. The latter was also observed in some primates by others and might therefore be of a more general validity.
|
|
