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Circadian phase resetting by a single short-duration light exposure.

ABSTRACT: BACKGROUND. In humans, a single light exposure of 12 minutes and multiple-millisecond light exposures can shift the phase of the circadian pacemaker. We investigated the response of the human circadian pacemaker to a single 15-second or 2-minute light pulse administered during the biological night. METHODS. Twenty-six healthy individuals participated in a 9-day inpatient protocol that included assessment of dim light melatonin onset time (DLMO time) before and after exposure to a single 15-second (n = 8) or 2-minute (n = 12) pulse of bright light (9,500 lux; 4,100 K fluorescent) or control background dim light (<3 lux; n = 6). Phase shifts were calculated as the difference in clock time between the two phase estimates. RESULTS. Both 15-second and 2-minute exposures induced phase delay shifts [median (± SD)] of -34.8 ± 47.2 minutes and -45.4 ± 28.4 minutes, respectively, that were significantly (P = 0.04) greater than the control condition (advance shift: +22.3 ± 51.3 minutes) but were not significantly different from each other. Comparisons with historic data collected under the same conditions confirmed a nonlinear relationship between exposure duration and the magnitude of phase shift. CONCLUSIONS. Our results underscore the exquisite sensitivity of the human pacemaker to even short-duration single exposures to light. These findings may have real-world implications for circadian disruption induced by exposure to brief light stimuli at night. TRIAL REGISTRATION. The study was registered as a clinical trial on www.clinicaltrials.org, NCT #01330992. FUNDING. Funding for this study was provided by NSBRI HFP02802 and NIH P01-AG09975, R01-HL114088 (EBK), RC2-HL101340-0 (EBK, SWL, SAR, REK), K02-HD045459 (EBK), K24-HL105664 (EBK), T32-HL07901 (MSH, SAR), HL094654 (CAC), and AG044416 (JFD). The project described was supported by NIH grant 1UL1 TR001102-01, 8UL1TR000170-05, UL1 RR 025758, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science.

SUBMITTER: Rahman SA

PROVIDER: S-EPMC5374060 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Circadian phase resetting by a single short-duration light exposure.

Rahman Shadab A SA St Hilaire Melissa A MA Chang Anne-Marie AM Santhi Nayantara N Duffy Jeanne F JF Kronauer Richard E RE Czeisler Charles A CA Lockley Steven W SW Klerman Elizabeth B EB

JCI insight 20170406 7

<b>BACKGROUND.</b> In humans, a single light exposure of 12 minutes and multiple-millisecond light exposures can shift the phase of the circadian pacemaker. We investigated the response of the human circadian pacemaker to a single 15-second or 2-minute light pulse administered during the biological night. <b>METHODS.</b> Twenty-six healthy individuals participated in a 9-day inpatient protocol that included assessment of dim light melatonin onset time (DLMO time) before and after exposure to a s ...[more]

PMID: 28405608

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Project description:The environmental light-dark cycle is the dominant cue that maintains 24-h biological rhythms in multicellular organisms. In Drosophila, light entrainment is mediated by the photosensitive protein CRYPTOCHROME, but the role and extent of transcription regulation in light resetting of the dipteran clock is yet unknown. Given the broad transcriptional changes in response to light previously identified in mammals, we have sought to analyse light-induced global transcriptional changes in the fly's head by using Affymetrix microarrays. Flies were subjected to a 30-min light pulse during the early night (3 h after lights-off), a stimulus which causes a substantial phase delay of the circadian rhythm. We then analysed changes in gene expression 1 h after the light stimulus.We identified 200 genes whose transcripts were significantly altered in response to the light pulse at a false discovery rate cut-off of 10%. Analysis of these genes and their biological functions suggests the involvement of at least six biological processes in light-induced delay phase shifts of rhythmic activities. These processes include signalling, ion channel transport, receptor activity, synaptic organisation, signal transduction, and chromatin remodelling. Using RNAi, the expression of 22 genes was downregulated in the clock neurons, leading to significant effects on circadian output. For example, while continuous light normally causes arrhythmicity in wild-type flies, the knockdown of Kr-h1, Nipped-A, Thor, nrv1, Nf1, CG11155 (ionotropic glutamate receptor), and Fmr1 resulted in flies that were rhythmic, suggesting a disruption in the light input pathway to the clock.Our analysis provides a first insight into the early responsive genes that are activated by light and their contribution to light resetting of the Drosophila clock. The analysis suggests multiple domains and pathways that might be associated with light entrainment, including a mechanism that was represented by a light-activated set of chromatin remodelling genes.

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Circadian phase resetting by a single short-duration light exposure.

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Circadian phase resetting by a single short-duration light exposure.

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