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Author LeGates, T.A.; Altimus, C.M.; Wang, H.; Lee, H.-K.; Yang, S.; Zhao, H.; Kirkwood, A.; Weber, E.T.; Hattar, S.
Title Aberrant light directly impairs mood and learning through melanopsin-expressing neurons Type Journal Article
Year 2012 Publication Nature Abbreviated Journal Nature
Volume 491 Issue 7425 Pages (down) 594-598
Keywords Affect/drug effects/physiology/*radiation effects; Animals; Antidepressive Agents/pharmacology; Body Temperature Regulation/physiology/radiation effects; Circadian Rhythm/physiology; Cognition/drug effects/physiology/radiation effects; Corticosterone/metabolism; Depression/etiology/physiopathology; Desipramine/pharmacology; Fluoxetine/pharmacology; Learning/drug effects/physiology/*radiation effects; *Light; Long-Term Potentiation/drug effects; Male; Memory/physiology/radiation effects; Mice; Photoperiod; Retinal Ganglion Cells/drug effects/*metabolism/*radiation effects; *Rod Opsins/analysis; Sleep/physiology; Wakefulness/physiology
Abstract The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.
Address Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA
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 0028-0836 ISBN Medium
Area Expedition Conference
Notes PMID:23151476; PMCID:PMC3549331 Approved no
Call Number IDA @ john @ Serial 238
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Author Boivin, D.B.; Duffy, J.F.; Kronauer, R.E.; Czeisler, C.A.
Title Dose-response relationships for resetting of human circadian clock by light Type Journal Article
Year 1996 Publication Nature Abbreviated Journal Nature
Volume 379 Issue 6565 Pages (down) 540-542
Keywords Human Health; Adult; Body Temperature; Circadian Rhythm/*radiation effects; Dose-Response Relationship, Radiation; Humans; *Light; Male; NASA Discipline Number 18-10; NASA Discipline Regulatory Physiology; NASA Program Space Physiology and Countermeasures; Non-NASA Center
Abstract Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.
Address Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
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 0028-0836 ISBN Medium
Area Expedition Conference
Notes PMID:8596632 Approved no
Call Number LoNNe @ kagoburian @ Serial 722
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Author Filipski, E.; Li, X.M.; Levi, F.
Title Disruption of circadian coordination and malignant growth Type Journal Article
Year 2006 Publication Cancer Causes & Control : CCC Abbreviated Journal Cancer Causes Control
Volume 17 Issue 4 Pages (down) 509-514
Keywords Human Health; Animals; Biological Clocks; Body Temperature; Cell Cycle Proteins; Cell Line, Tumor; Chronobiology Disorders/*complications/physiopathology; Circadian Rhythm; Corticosterone/blood; DNA-Binding Proteins/metabolism; Jet Lag Syndrome/complications/physiopathology; Lymphocyte Count; Mice; Neoplasm Transplantation; Nuclear Proteins/metabolism; Nuclear Receptor Subfamily 1, Group D, Member 1; Osteosarcoma/*pathology/physiopathology; Pancreatic Neoplasms/*pathology/physiopathology; Period Circadian Proteins; Receptors, Cytoplasmic and Nuclear/metabolism; Suprachiasmatic Nucleus/physiopathology; Transcription Factors/metabolism
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.
Address INSERM E 354 Cancer Chronotherapeutics, Hopital Paul Brousse, Villejuif, France. filipski@vjf.inserm.fr
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:16596304 Approved no
Call Number LoNNe @ kagoburian @ Serial 748
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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 Lack, L.C.; Gradisar, M.; Van Someren, E.J.W.; Wright, H.R.; Lushington, K.
Title The relationship between insomnia and body temperatures Type Journal Article
Year 2008 Publication Sleep Medicine Reviews Abbreviated Journal Sleep Med Rev
Volume 12 Issue 4 Pages (down) 307-317
Keywords Human Health; Arousal/physiology; Body Temperature Regulation/*physiology; Circadian Rhythm/physiology; Homeostasis/physiology; Humans; Melatonin/blood; Phototherapy; Skin Temperature/physiology; Sleep Disorders, Circadian Rhythm/physiopathology/therapy; Sleep Initiation and Maintenance Disorders/*physiopathology/therapy; Sympathetic Nervous System/physiopathology; Wakefulness/physiology
Abstract Sleepiness and sleep propensity are strongly influenced by our circadian clock as indicated by many circadian rhythms, most commonly by that of core body temperature. Sleep is most conducive in the temperature minimum phase, but is inhibited in a “wake maintenance zone” before the minimum phase, and is disrupted in a zone following that phase. Different types of insomnia symptoms have been associated with abnormalities of the body temperature rhythm. Sleep onset insomnia is associated with a delayed temperature rhythm presumably, at least partly, because sleep is attempted during a delayed evening wake maintenance zone. Morning bright light has been used to phase advance circadian rhythms and successfully treat sleep onset insomnia. Conversely, early morning awakening insomnia has been associated with a phase advanced temperature rhythm and has been successfully treated with the phase delaying effects of evening bright light. Sleep maintenance insomnia has been associated not with a circadian rhythm timing abnormality, but with nocturnally elevated core body temperature. Combination of sleep onset and maintenance insomnia has been associated with a 24-h elevation of core body temperature supporting the chronic hyper-arousal model of insomnia. The possibility that these last two types of insomnia may be related to impaired thermoregulation, particularly a reduced ability to dissipate body heat from distal skin areas, has not been consistently supported in laboratory studies. Further studies of thermoregulation are needed in the typical home environment in which the insomnia is most evident.
Address School of Psychology, Flinders University, South Australia, Australia. leon.lack@flinders.edu.au
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 1087-0792 ISBN Medium
Area Expedition Conference
Notes PMID:18603220 Approved no
Call Number LoNNe @ kagoburian @ Serial 775
Permanent link to this record