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Author Walbeek, T.J.; Harrison, E.M.; Soler, R.R.; Gorman, M.R.
Title Enhanced Circadian Entrainment in Mice and Its Utility under Human Shiftwork Schedules Type Journal Article
Year 2019 Publication Clocks & Sleep Abbreviated Journal Clocks & Sleep
Volume 1 Issue 3 Pages 394-413
Keywords (up) Animals
Abstract The circadian system is generally considered to be incapable of adjusting to rapid changes in sleep/work demands. In shiftworkers this leads to chronic circadian disruption and sleep loss, which together predict underperformance at work and negative health consequences. Two distinct experimental protocols have been proposed to increase circadian flexibility in rodents using dim light at night: rhythm bifurcation and T-cycle (i.e., day length) entrainment. Successful translation of such protocols to human shiftworkers could facilitate alignment of internal time with external demands. To assess entrainment flexibility following bifurcation and exposure to T-cycles, mice in Study 1 were repeatedly phase-shifted. Mice from experimental conditions rapidly phase-shifted their activity, while control mice showed expected transient misalignment. In Study 2 and 3, mice followed a several weeks-long intervention designed to model a modified DuPont or Continental shiftwork schedule, respectively. For both schedules, bifurcation and nocturnal dim lighting reduced circadian misalignment. Together, these studies demonstrate proof of concept that mammalian circadian systems can be rendered sufficiently flexible to adapt to multiple, rapidly changing shiftwork schedules. Flexible adaptation to exotic light-dark cycles likely relies on entrainment mechanisms that are distinct from traditional entrainment.
Address
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Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2624-5175 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number GFZ @ kyba @ Serial 2661
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Author Wang, H.-B.; Whittaker, D.S.; Truong, D.; Mulji, A.K.; Ghiani, C.A.; Loh, D.H.; Colwell, C.S.
Title Blue light therapy improves circadian dysfunction as well as motor symptoms in two mouse models of Huntington's disease Type Journal Article
Year 2017 Publication Neurobiology of Sleep and Circadian Rhythms Abbreviated Journal Neurobiology of Sleep and Circadian Rhythms
Volume 2 Issue Pages 39-52
Keywords (up) animals; Human Health
Abstract Patients with Huntington's disease (HD) exhibit movement disorders, psychiatric disturbance and cognitive impairments as the disease progresses. Abnormal sleep/wake cycles are common among HD patients with reports of delayed sleep onset, fatigue during the day, and a delayed pattern of melatonin secretion all of which suggest circadian dysfunction. Mouse models of HD confirm disrupted circadian rhythms with pathophysiology found in the central circadian clock (suprachiasmatic nucleus). Importantly, circadian dysfunction manifests early in disease, even before the classic motor symptoms, in both patients and mouse models. Therefore, we hypothesize that the circadian dysfunction may interact with the disease pathology and exacerbate the HD symptoms. If correct, early intervention may benefit patients and delay disease progression. One test of this hypothesis is to determine whether light therapy designed to strengthen this intrinsic timing system can delay the disease progression in mouse models. Therefore, we determined the impact of blue wavelength-enriched light on two HD models: the BACHD and Q175 mice. Both models received 6 hours of blue-light at the beginning of their daily light cycle for 3 months. After treatment, both genotypes showed improvements in their locomotor activity rhythm without significant change to their sleep behavior. Critically, treated mice of both lines exhibited improved motor performance compared to untreated controls. Focusing on the Q175 genotype, we sought to determine whether the treatment altered signaling pathways in brain regions known to be impacted by HD using NanoString gene expression assays. We found that the expression of several HD relevant markers was altered in the striatum and cortex of the treated mice. Our study demonstrates that strengthening the circadian system can delay the progression of HD in pre-clinical models. This work suggests that lighting conditions should be considered when managing treatment of HD and other neurodegenerative disorders.
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Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2451-9944 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number LoNNe @ kyba @ Serial 1626
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Author Chang, A.-M.; Scheer, F.A.J.L.; Czeisler, C.A.; Aeschbach, D.
Title Direct effects of light on alertness, vigilance, and the waking electroencephalogram in humans depend on prior light history Type Journal Article
Year 2013 Publication Sleep Abbreviated Journal Sleep
Volume 36 Issue 8 Pages 1239-1246
Keywords (up) Arousal/*radiation effects; Attention/radiation effects; Cross-Over Studies; *Electroencephalography; Female; Humans; *Light; Male; Melatonin/blood/physiology; Psychomotor Performance/radiation effects; Reaction Time; Wakefulness/*radiation effects; Young Adult; Light history; alertness and performance; light exposure
Abstract STUDY OBJECTIVES: Light can induce an acute alerting response in humans; however, it is unknown whether the magnitude of this response is simply a function of the absolute illuminance of the light itself, or whether it depends on illuminance history preceding the stimulus. Here, we compared the effects of illuminance history on the alerting response to a subsequent light stimulus. DESIGN: A randomized, crossover design was used to compare the effect of two illuminance histories (1 lux vs. 90 lux) on the alerting response to a 6.5-h 90-lux light stimulus during the biological night. SETTING: Intensive Physiologic Monitoring Unit, Brigham and Women's Hospital, Boston, MA. PARTICIPANTS: Fourteen healthy young adults (6 F; 23.5 +/- 2.9 years). INTERVENTIONS: Participants were administered two 6.5-h light exposures (LE) of 90 lux during the biological night. For 3 days prior to each LE, participants were exposed to either 1 lux or 90 lux during the wake episode. MEASUREMENTS AND RESULTS: The alerting response to light was assessed using subjective sleepiness ratings, lapses of attention, and reaction times as measured with an auditory psychomotor vigilance task, as well as power density in the delta/theta range of the waking EEG. The alerting response to light was greater and lasted longer when the LE followed exposure to 1 lux compared to 90 lux light. CONCLUSION: The magnitude and duration of the alerting effect of light at night depends on the illuminance history and appears to be subject to sensitization and adaptation.
Address Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. amchang@rics.bwh.harvard.edu
Corporate Author Thesis
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Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0161-8105 ISBN Medium
Area Expedition Conference
Notes PMID:23904684; PMCID:PMC3700721 Approved no
Call Number IDA @ john @ Serial 145
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Author Kayaba, M.; Iwayama, K.; Ogata, H.; Seya, Y.; Tokuyama, K.; Satoh, M.
Title Drowsiness and low energy metabolism in the following morning induced by nocturnal blue light exposure Type Journal Article
Year 2013 Publication Sleep Medicine Abbreviated Journal Sleep Medicine
Volume 14 Issue Pages e166-e167
Keywords (up) blue light; light exposure; light at night; circadian disruption; drowsiness; melatonin; metabolism; sleep
Abstract Introduction

Evening light exposure debilitates the circadian rhythm and elicits sleep disturbance. Blue light peak wavelengths, around 460 nm, suppress melatonin secretion via the non-image-forming system. The effects of nocturnal blue light exposure on sleep have been reported to be specific but rather small (Münch, 2008). This study was designed to assess the effect of nocturnal blue light exposure on sleep and energy metabolism until noon the next day.

Materials and methods

Nine healthy male volunteers aged between 21 and 25 participated in this study which had a balanced cross-over design with intrasubject comparisons. After 2 h dark adaptation, the subjects were exposed to blue light or no light for 2 h. The peak wavelength of the blue LED was 465 nm, and the horizontal irradiance of the blue light at the height of eye was at 7.02fÊW/cm2. Sleep was recorded polysomnographically, and energy metabolism was measured with a whole body indirect calorimeter.

Results

There were no significant differences in sleep architecture and energy metabolism during the night. However, dozing (stages 1 and 2) was significantly higher (26.0 < 29.4 vs 6.3 < 8.1 min, P < 0.05), and energy expenditure, O2 consumption, CO2 production and the thermic effect of food (increase in energy expenditure after breakfast) were significantly lower the following morning in the blue light exposure subjects.

Conclusion

Contrary to our expectation, sleep architecture and energy metabolism during sleep were not affected by evening exposure to blue light. It might be due to our milder intervention by which subjects in a sitting position did not gaze at the light source set on the ceiling, while the subjects in previous studies directly received brighter light via custom built goggles (Cajochen, 2005; Münch, 2008) or gazed at a light source under the influence of mydriatic agents to dilate pupils (Brainard, 2001). New findings of the present study were that dozing (stages 1 and 2) was significantly increased, and energy metabolism was significantly lower the following morning in blue light exposed subjects. This suggests that modulation of the circadian rhythm is affected by nocturnal blue light exposure and the effect continues in the following daytime even if the intervention was mild.
Address University of Tsukuba, Graduate School of Comprehensive Human Sciences, Japan
Corporate Author Thesis
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Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1389-9457 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number IDA @ john @ Serial 349
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Author Smith, M.R.; Eastman, C.I.
Title Shift work: health, performance and safety problems, traditional countermeasures, and innovative management strategies to reduce circadian misalignment Type Journal Article
Year 2012 Publication Nature and Science of Sleep Abbreviated Journal Nat Sci Sleep
Volume 4 Issue Pages 111-132
Keywords (up) bright light; circadian rhythms; melatonin; night work; phase-shifting; sleep
Abstract There are three mechanisms that may contribute to the health, performance, and safety problems associated with night-shift work: (1) circadian misalignment between the internal circadian clock and activities such as work, sleep, and eating, (2) chronic, partial sleep deprivation, and (3) melatonin suppression by light at night. The typical countermeasures, such as caffeine, naps, and melatonin (for its sleep-promoting effect), along with education about sleep and circadian rhythms, are the components of most fatigue risk-management plans. We contend that these, while better than nothing, are not enough because they do not address the underlying cause of the problems, which is circadian misalignment. We explain how to reset (phase-shift) the circadian clock to partially align with the night-work, day-sleep schedule, and thus reduce circadian misalignment while preserving sleep and functioning on days off. This involves controlling light and dark using outdoor light exposure, sunglasses, sleep in the dark, and a little bright light during night work. We present a diagram of a sleep-and-light schedule to reduce circadian misalignment in permanent night work, or a rotation between evenings and nights, and give practical advice on how to implement this type of plan.
Address Biological Rhythms Research Laboratory, Rush University Medical Center, Chicago, IL, 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 1179-1608 ISBN Medium
Area Expedition Conference
Notes PMID:23620685; PMCID:PMC3630978 Approved no
Call Number IDA @ john @ Serial 149
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