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Author Chellappa, S.L.; Viola, A.U.; Schmidt, C.; Bachmann, V.; Gabel, V.; Maire, M.; Reichert, C.F.; Valomon, A.; Gotz, T.; Landolt, H.-P.; Cajochen, C.
Title Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3 Type Journal Article
Year 2012 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 97 Issue 3 Pages (down) E433-7
Keywords Adult; Alleles; Cross-Over Studies; Female; Genotype; Homozygote; Humans; *Light; Male; Melatonin/*blood/genetics; *Minisatellite Repeats; Period Circadian Proteins/*genetics; *Polymorphism, Genetic; Questionnaires; Sleep/genetics; Wakefulness/*genetics
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.
Address Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstrasse 27, CH-4012 Basel, Switzerland
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:22188742 Approved no
Call Number IDA @ john @ Serial 301
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Author Brainard, G.C.; Sliney, D.; Hanifin, J.P.; Glickman, G.; Byrne, B.; Greeson, J.M.; Jasser, S.; Gerner, E.; Rollag, M.D.
Title Sensitivity of the human circadian system to short-wavelength (420-nm) light Type Journal Article
Year 2008 Publication Journal of Biological Rhythms Abbreviated Journal J Biol Rhythms
Volume 23 Issue 5 Pages (down) 379-386
Keywords Human Health; Adult; Circadian Rhythm/*radiation effects; Female; Humans; *Light; Male; Melatonin/metabolism; Models, Biological; Neurosecretory Systems; Photons; Pineal Gland/metabolism; Retinal Ganglion Cells/*metabolism; Vision, Ocular
Abstract The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.
Address Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. george.brainard@jefferson.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0748-7304 ISBN Medium
Area Expedition Conference
Notes PMID:18838601 Approved no
Call Number LoNNe @ kagoburian @ Serial 724
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Author Bullough, J.D.; Rea, M.S.; Figueiro, M.G.
Title Of mice and women: light as a circadian stimulus in breast cancer research Type Journal Article
Year 2006 Publication Cancer Causes & Control : CCC Abbreviated Journal Cancer Causes Control
Volume 17 Issue 4 Pages (down) 375-383
Keywords Human Health; Animals; Breast Neoplasms/*physiopathology; *Circadian Rhythm; *Disease Models, Animal; Female; Humans; *Light; Light Signal Transduction; Mammary Neoplasms, Animal/*physiopathology; Melatonin/metabolism; Mice; Muridae/metabolism
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.
Address Lighting Research Center, Rensselaer Polytechnic Institute, 21 Union Street, Troy, NY 12180, USA. bulloj@rpi.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0957-5243 ISBN Medium
Area Expedition Conference
Notes PMID:16596289 Approved no
Call Number LoNNe @ kagoburian @ Serial 726
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Author Ruger, M.; St Hilaire, M.A.; Brainard, G.C.; Khalsa, S.-B.S.; Kronauer, R.E.; Czeisler, C.A.; Lockley, S.W.
Title Human phase response curve to a single 6.5 h pulse of short-wavelength light Type Journal Article
Year 2013 Publication The Journal of Physiology Abbreviated Journal J Physiol
Volume 591 Issue Pt 1 Pages (down) 353-363
Keywords Adolescent; Adult; Body Temperature; Circadian Rhythm/*physiology; Female; Humans; *Light; Male; Melatonin/physiology; Young Adult; blue light; melatonin; photic response; whort-wavelength
Abstract The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a phase response curve (PRC). Previous PRCs in humans have utilized high-intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive to short-wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol. Eighteen young healthy participants (18-30 years) were studied for 9-10 days in a time-free environment. The protocol included three baseline days followed by a constant routine (CR) to assess initial circadian phase. Following this CR, participants were exposed to a 6.5 h 480 nm light exposure (11.8 muW cm(-2), 11.2 lux) following mydriasis via a modified Ganzfeld dome. A second CR was conducted following the light exposure to re-assess circadian phase. Phase shifts were calculated from the difference in dim light melatonin onset (DLMO) between CRs. Exposure to 6.5 h of 480 nm light resets the circadian pacemaker according to a conventional type 1 PRC with fitted maximum delays and advances of -2.6 h and 1.3 h, respectively. The 480 nm PRC induced approximately 75% of the response of the 10,000 lux white light PRC. These results may contribute to a re-evaluation of dosing guidelines for clinical light therapy and the use of light as a fatigue countermeasure.
Address Circadian Physiology Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. mrueger@rics.bwh.harvard.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3751 ISBN Medium
Area Expedition Conference
Notes PMID:23090946; PMCID:PMC3630790 Approved no
Call Number IDA @ john @ Serial 239
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Author Srinivasan, V.; Spence, D.W.; Pandi-Perumal, S.R.; Trakht, I.; Esquifino, A.I.; Cardinali, D.P.; Maestroni, G.J.
Title Melatonin, environmental light, and breast cancer Type Journal Article
Year 2008 Publication Breast Cancer Research and Treatment Abbreviated Journal Breast Cancer Res Treat
Volume 108 Issue 3 Pages (down) 339-350
Keywords Human Health; Breast Neoplasms/*etiology/*physiopathology; Circadian Rhythm/physiology; Female; Humans; Light; Lighting/*adverse effects; Melatonin/*physiology; Occupational Exposure/adverse effects
Abstract Although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Studies on the 7,12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human breast cancer indicate that melatonin is effective in reducing cancer development. In vitro studies in MCF-7 human breast cancer cell line have shown that melatonin exerts its anticarcinogenic actions through a variety of mechanisms, and that it is most effective in estrogen receptor (ER) alpha-positive breast cancer cells. Melatonin suppresses ER gene, modulates several estrogen dependent regulatory proteins and pro-oncogenes, inhibits cell proliferation, and impairs the metastatic capacity of MCF-7 human breast cancer cells. The anticarcinogenic action on MCF-7 cells has been demonstrated at the physiological concentrations of melatonin attained at night, suggesting thereby that melatonin acts like an endogenous antiestrogen. Melatonin also decreases the formation of estrogens from androgens via aromatase inhibition. Circulating melatonin levels are abnormally low in ER-positive breast cancer patients thereby supporting the melatonin hypothesis for breast cancer in shift working women. It has been postulated that enhanced endogenous melatonin secretion is responsible for the beneficial effects of meditation as a form of psychosocial intervention that helps breast cancer patients.
Address Department of Physiology, School of Medical Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0167-6806 ISBN Medium
Area Expedition Conference
Notes PMID:17541739 Approved no
Call Number LoNNe @ kagoburian @ Serial 815
Permanent link to this record