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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 (up) Neurobiology of Sleep and Circadian Rhythms Abbreviated Journal Neurobiology of Sleep and Circadian Rhythms
Volume 2 Issue Pages 39-52
Keywords 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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ISSN 2451-9944 ISBN Medium
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Notes Approved no
Call Number LoNNe @ kyba @ Serial 1626
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Author Akacem, L.D.; Wright, K.P.J.; LeBourgeois, M.K.
Title Bedtime and evening light exposure influence circadian timing in preschool-age children: A field study Type Journal Article
Year 2016 Publication (up) Neurobiology of Sleep and Circadian Rhythms Abbreviated Journal Neurobiol Sleep Circadian Rhythms
Volume 1 Issue 2 Pages 27-31
Keywords Human Health
Abstract Light exposure and sleep timing are two factors that influence inter-individual variability in the timing of the human circadian clock. The aim of this study was to quantify the degree to which evening light exposure predicts variance in circadian timing over and above bedtime alone in preschool children. Participants were 21 children ages 4.5-5.0 years (4.7 +/- 0.2 years; 9 females). Children followed their typical sleep schedules for 4 days during which time they wore a wrist actigraph to assess sleep timing and a pendant light meter to measure minute-by-minute illuminance levels in lux. On the 5th day, children participated in an in-home dim-light melatonin onset (DLMO) assessment. Light exposure in the 2 h before bedtime was averaged and aggregated across the 4 nights preceding the DLMO assessment. Mean DLMO and bedtime were 19:22 +/- 01:04 and 20:07 +/- 00:46, respectively. Average evening light exposure was 710.1 +/- 1418.2 lux. Children with later bedtimes (lights-off time) had more delayed melatonin onset times (r=0.61, p=0.002). Evening light exposure was not independently associated with DLMO (r=0.32, p=0.08); however, a partial correlation between evening light exposure and DLMO when controlling for bedtime yielded a positive correlation (r=0.46, p=0.02). Bedtime explained 37.3% of the variance in the timing of DLMO, and evening light exposure accounted for an additional 13.3% of the variance. These findings represent an important step in understanding factors that influence circadian phase in preschool-age children and have implications for understanding a modifiable pathway that may underlie late sleep timing and the development of evening settling problems in early childhood.
Address Sleep and Development Laboratory, Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA
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Language English Summary Language Original Title
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Series Volume Series Issue Edition
ISSN 2451-9944 ISBN Medium
Area Expedition Conference
Notes PMID:28042611; PMCID:PMC5193478 Approved no
Call Number LoNNe @ kyba @ Serial 1755
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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 (up) Sleep Abbreviated Journal Sleep
Volume 36 Issue 8 Pages 1239-1246
Keywords 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
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ISSN 0161-8105 ISBN Medium
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Notes PMID:23904684; PMCID:PMC3700721 Approved no
Call Number IDA @ john @ Serial 145
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Author Kessel, L.; Siganos, G.; Jorgensen, T.; Larsen, M.
Title Sleep disturbances are related to decreased transmission of blue light to the retina caused by lens yellowing Type Journal Article
Year 2011 Publication (up) Sleep Abbreviated Journal Sleep
Volume 34 Issue 9 Pages 1215-1219
Keywords Adult; Age Factors; Aging/*pathology/physiology; Circadian Rhythm/physiology; Cross-Sectional Studies; Female; Fluorometry; Humans; Lens, Crystalline/*pathology/physiopathology; *Light; Male; Middle Aged; Retina/*physiopathology; Risk Factors; *Scattering, Radiation; Sleep Disorders/*etiology; Circadian rhythm; cataract; melanopsin; sleep; blue light
Abstract STUDY OBJECTIVES: Sleep pattern and circadian rhythms are regulated via the retinohypothalamic tract in response to stimulation of a subset of retinal ganglion cells, predominantly by blue light (450-490 nm). With age, the transmission of blue light to the retina is reduced because of the aging process of the human lens, and this may impair the photoentrainment of circadian rhythm leading to sleep disorders. The aim of the study was to examine the association between lens aging and sleep disorders. DESIGN: Cross-sectional population based study. SETTING: The study was performed at the Research Center for Prevention and Health, Glostrup Hospital, Denmark and at the Department of Ophthalmology, Herlev Hospital, Denmark. PARTICIPANTS: An age- and sex-stratified sample of 970 persons aged 30 to 60 years of age drawn from a sample randomly selected from the background population. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Sleep disturbances were evaluated by a combination of questionnaire and the use of prescription sleeping medication. Lens aging (transmission and yellowing) was measured objectively by lens autofluorometry. The risk of sleep disturbances was significantly increased when the transmission of blue light to the retina was low, even after correction for the effect of age and other confounding factors such as smoking habits, diabetes mellitus, gender, and the risk of ischemic heart disease (P < 0.0001). CONCLUSIONS: Filtration of blue light by the aging lens was significantly associated with an increased risk of sleep disturbances. We propose that this is a result of disturbance of photoentrainment of circadian rhythms.
Address Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark. line.kessel@dadlnet.dk
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ISSN 0161-8105 ISBN Medium
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Notes PMID:21886359; PMCID:PMC3157663 Approved no
Call Number IDA @ john @ Serial 344
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Author Wams, E.J.; Woelders, T.; Marring, I.; van Rosmalen, L.; Beersma, D.G.M.; Gordijn, M.C.M.; Hut, R.A.
Title Linking Light Exposure and Subsequent Sleep: A Field Polysomnography Study in Humans Type Journal Article
Year 2017 Publication (up) Sleep Abbreviated Journal Sleep
Volume 40 Issue 12 Pages
Keywords actigraphy; chronobiology; circadian rhythms; scoring; sleep/wake mechanisms
Abstract Study objectives: To determine the effect of light exposure on subsequent sleep characteristics under ambulatory field conditions. Methods: Twenty healthy participants were fitted with ambulatory polysomnography (PSG) and wrist-actigraphs to assess light exposure, rest-activity, sleep quality, timing, and architecture. Laboratory salivary dim-light melatonin onset was analyzed to determine endogenous circadian phase. Results: Later circadian clock phase was associated with lower intensity (R2 = 0.34, chi2(1) = 7.19, p < .01), later light exposure (quadratic, controlling for daylength, R2 = 0.47, chi2(3) = 32.38, p < .0001), and to later sleep timing (R2 = 0.71, chi2(1) = 20.39, p < .0001). Those with later first exposure to more than 10 lux of light had more awakenings during subsequent sleep (controlled for daylength, R2 = 0.36, chi2(2) = 8.66, p < .05). Those with later light exposure subsequently had a shorter latency to first rapid eye movement (REM) sleep episode (R2 = 0.21, chi2(1) = 5.77, p < .05). Those with less light exposure subsequently had a higher percentage of REM sleep (R2 = 0.43, chi2(2) = 13.90, p < .001) in a clock phase modulated manner. Slow-wave sleep accumulation was observed to be larger after preceding exposure to high maximal intensity and early first light exposure (p < .05). Conclusions: The quality and architecture of sleep is associated with preceding light exposure. We propose that light exposure timing and intensity do not only modulate circadian-driven aspects of sleep but also homeostatic sleep pressure. These novel ambulatory PSG findings are the first to highlight the direct relationship between light and subsequent sleep, combining knowledge of homeostatic and circadian regulation of sleep by light. Upon confirmation by interventional studies, this hypothesis could change current understanding of sleep regulation and its relationship to prior light exposure. Clinical trial details: This study was not a clinical trial. The study was ethically approved and nationally registered (NL48468.042.14).
Address Chronobiology Unit, Groningen Institute for Evolutionary Life Sciences, University of Groningen, The Netherlands
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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:29040758; PMCID:PMC5806586 Approved no
Call Number GFZ @ kyba @ Serial 1885
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