Consequences of Artificial Light Exposure for Healthy Physiology

Lead Research Organisation: University of Oxford
Department Name: Clinical Neurosciences

Abstract

CIRCADIAN RHYTHMS
Life on Earth has evolved under a rhythmically changing cycle of day and night. As a result, virtually all organisms have evolved internal biological clocks with a period of ~24h. These circadian clocks (from the Latin 'circa diem', or around a day) enable organisms to anticipate and adapt to predictable changes in their environment. In mammals, the master circadian clock is located in the suprachiasmatic nuclei (SCN) in the brain. Rhythms in the SCN are generated by a genetic clock mechanism. This clock mechanism is found in cells throughout our bodies, regulating tissue-specific functions.

CIRCADIAN EFFECTS OF LIGHT
A clock is of no use unless it can be set to the correct time. The SCN receives light information from the eye, which contains light sensitive cells (photoreceptors) which synchronise circadian rhythms to the external light/dark (LD) cycle. The retinatains two classes of visual photoreceptor - the rods (which mediate night-time vision) and cones (which give us our day-time colour vision). Work over the last two decades has led to the discovery of a novel retinal photoreceptor system, consisting of a subset of photosensitive retinal ganglion cells expressing the blue-light sensitive protein melanopsin.

DIM LIGHT IN THE EVENING
Research on the effects of light on circadian rhythms has led to a remarkable public awareness of the circadian effects of evening light exposure, with a particular concern about blue-enriched light from home lighting and mobile devices. Exposure to dim light in the evening results in a misalignment of human circadian rhythms. Our recent work has shown that this circadian effect also occurs in mice and is accompanied by misalignment of circadian clocks found throughout our bodies, including in the liver, heart and brain. The long-term effects of such light exposure are unknown. However, under other study conditions where similar misalignment is seen, changes in body weight and metabolism, heart function and learning and memory occur. Given that artificial light exposure is an unavoidable feature of modern life, this has potentially important implications for health.

PROPOSED STUDIES
This project will investigate the long-term consequences of evening light exposure. Specifically, we will study mice housed for 3 months under dim light in the evening conditions to investigate how their body weight, metabolism and heart function change. We will also study hormones and blood chemistry for changes. Mice will also undergo a range of behavioural tests to see if dim light in the evening alters learning, memory and mood. By using brain imaging, we can see if changes in specific brain regions occur, as well as how their connections with other areas of the brain change. To determine if these effects occur due to the circadian clock being unable to adapt, we will study mice that lack circadian clocks, with the prediction that these animals will be unaffected. We will also study changes in the activity of neurons at the level of the eye and the SCN master clock. We will then study the patterns of gene expression in the SCN master clock, as well as several key tissues throughout the body to see how these are affected. By studying common regulators of gene expression, this will help us understand the mechanisms by which dim light in the evening affects clocks throughout the body. Finally, we will test how changing the pattern of light exposure may avoid the detrimental circadian effects of light.

OUTCOMES
We are exposed to artificial lighting throughout our lives with little appreciation of its biological effects. This proposal will provide critical information about the long-term consequences of the modern light environment and the biological mechanisms underlying these responses. Critically, this work will also provide new data to help devise and test strategies to avoid these detrimental effects.

Technical Summary

This project addresses the specific mechanisms by which the modern light environment disrupts circadian rhythms. The widespread use of artificial lighting and light-emitting mobile devices means that we are increasingly exposed to dim light on an evening (DLE), when our circadian clocks are most sensitive to light. Accumulating evidence suggests that this can misalign circadian clocks found throughout our bodies, with negative consequences for long-term health. However, the extent of these effects on healthy physiology and our understanding of the mechanisms underlying them are limited. This information is critical if we are to develop and test strategies to mitigate these risks.

This proposal will characterise the long-term effects of DLE on metabolic, cardiovascular and cognitive function. Using a range of different phenotyping assays, we will determine the health consequence of long-term DLE (12 weeks). This will be complemented by small animal MRI to study changes in brain morphology and connectivity. We hypothesise that the detrimental effects of DLE occur via a mismatch between circadian rhythms and environmental time. To test this, we will study mice lacking circadian rhythms, where we expect the effects to be reduced. We will also study the effects of DLE on neuronal responses at the level of the retina and suprachiasmatic nuclei (SCN). We will use RNAseq to study the effects of DLE on gene expression at the level of the SCN, liver, heart, adrenal and hippocampus, using analysis of circadian transcriptional regulators to identify key mechanisms. Finally, we will investigate if interventions designed to reduce the circadian effects of DLE are effective in preventing these long-term health consequences.
 
Description Brain Networks Underlying Sleep and Circadian Rhythm Disruption (SCRD) in Mental Health
Amount £2,998,922 (GBP)
Funding ID 226975/Z/23/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2023 
End 05/2028
 
Title SnackerTracker 
Description We have developed a system for measuring home cage foot seeking behaviour and food intake. This system is wireless and can send data to a web address so animal feeding can be monitored in real time 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2023 
Provided To Others? No  
Impact We have identified rhythms in feeding, even in the absence of circadian rhythms. This has been very valuable for investigating the role of feeding in circadian disruption. We have also had interest from other groups, such as those working on the microbiome. 
 
Title Validation of DVC for circadian and sleep phenotyping 
Description In collaboration with Tecniplast, we are testing their digital ventilated cage (DVC) system for circadian phenotyping as well as validating this approach for non invasive measurement of sleep. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2022 
Provided To Others? No  
Impact This work is still in progress, but the collaboration has already led to one publication on the effects of home cage lighting on mouse activity. Circadian validation is complete and we have all data on validation of sleep in comparison with gold standard electroencephalography (EEG). 
URL https://www.frontiersin.org/articles/10.3389/fnins.2021.832535/full
 
Description Oxford BMS 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Working in collaboration with our Biomedical Services (BMS) department, we are establishing a central facility for home cage monitoring for all Oxford animal users. This is based around the Tecniplast DVC system (now purchased by Oxford BMS), and will have a dedicated team of technicians and scientists to support researchers to use home cage monitoring for both scientific and welfare benefits.
Collaborator Contribution Prof Peirson is the scientific lead and will provide guidance on the use of home cage monitoring, including experimental design and statistics as well as data interpretation. This has the potential to provide additional scientific data as well as to identify the welfare impacts of procedures and to identify earlier humane endpoints.
Impact Additional papers in preparation and website in preparation
Start Year 2022
 
Description 3rd Circadian Photometry Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 25 scientific experts were gathered together for a 3 day workshop to establish new methods for measuring light for laboratory animals. This included experts in light, circadian rhythms, vision and lab animal welfare. This resulted in writing a guidance paper and providing new tools for light measurement (in press in PLOS Biology).
Year(s) Of Engagement Activity 2023