Investigating the mechanisms mediating circadian disruption by the modern light environment

Thesis

The circadian system regulates daily rhythms in physiology and behavior, with light as its primary entrainment cue. Modern light environments, characterized by decreased daytime light and increased evening artificial light, have been linked to circadian disruption and various health issues. This thesis investigated the effects of dim light in the evening (DLE) on circadian rhythms in mice. We established that both acute and chronic exposure to DLE (20 lux, ZT12-16) induces consistent phase delays in activity, sleep, and body temperature rhythms. This maintenance of internal synchrony with temporal reorganization suggests a coordinated realignment to the new dark onset. We observed sex-specific differences, with females showing greater vulnerability to metabolic disruptions despite more robust rhythms. To explore underlying mechanisms and discern the contribution of circadian disruption versus changes in sleep state during the dim phase, we combined sleep deprivation during the dim phase with transition to constant darkness. Animals free-ran from a delayed phase regardless of prior sleep during the dim light, demonstrating that DLE directly entrains the circadian clock through photic pathways independent of sleep state and masking effects. We then evaluated interventions to attenuate DLE effects. Neither varying daytime light intensity (20-500 lux) and supplementing violet light to target S-cone activation and melanopsin inhibition showed significant impact. Blue-blocking filters were ineffective at standard illuminance (20 lux), but significantly attenuated phase delays when combined with reduced light intensity (6 lux). These findings establish that the circadian system remains sensitive to modest evening illumination, with effects mediated through direct photic entrainment involving multiple photoreceptor classes. Comprehensive approaches addressing both spectral composition and light intensity may best mitigate the circadian impact of unavoidable evening light exposure. This work contributes to understanding how modern light environments affect biological timing and strategies to support circadian health.

Authors: Tir, S

• DOI: 10.5287/ora-y5zz2bxqr
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: blue-blocking filters; circadian disruption; artificial light; photoreceptors; dim light in the evening; circadian rhythms; sex differences
• Subjects: Sleep; Neurosciences; Circadian rhythms