Abstract

Healthy sleep supports robust development of the brain and behavior. Modern society presents a host of challenges that can impair and disrupt critical circadian rhythms that reinforce optimal physiological functioning, including the proper timing and consolidation of sleep. While the acute effects of inadequate sleep and disrupted circadian rhythms are being defined, the adverse developmental consequences of disrupted sleep and circadian rhythms are understudied. Here, we exposed mice to disrupting light–dark cycles from birth until weaning and demonstrate that such exposure has adverse impacts on brain and behavior as adults. Mice that experience early-life circadian disruption exhibit more anxiety-like behavior in the elevated plus maze, poorer spatial memory in the Morris Water Maze, and impaired working memory in a delayed match-to-sample task. Additionally, neuron morphology in the amygdala, hippocampus and prefrontal cortex is adversely impacted. Pyramidal cells in these areas had smaller dendritic fields, and pyramidal cells in the prefrontal cortex and hippocampus also exhibited diminished branching orders. Disrupted mice were also hyperactive as adults, but otherwise exhibited no alteration in adult circadian locomotor rhythms. These results highlight that circadian disruption early in life may have long lasting and far-reaching consequences for the development of behavior and the brain.

https://pubmed.ncbi.nlm.nih.gov/35513413/

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Abstract

Light plays a fundamental role in the ecology of organisms in nearly all habitats on Earth and is central for processes such as vision and the entrainment of the circadian clock. The poles represent extreme light regimes with an annual light cycle including periods of Midnight Sun and Polar Night. The Arctic Ocean extends to the North Pole, and marine light extremes reach their maximum extent in this habitat. During the Polar Night, traditional definitions of day and night and seasonal photoperiod become irrelevant since there are only “twilight” periods defined by the sun’s elevation below the horizon at midday; we term this “midday twilight.” Here, we characterize light across a latitudinal gradient (76.5° N to 81° N) during Polar Night in January. Our light measurements demonstrate that the classical solar diel light cycle dominant at lower latitudes is modulated during Arctic Polar Night by lunar and auroral components. We therefore question whether this particular ambient light environment is relevant to behavioral and visual processes. We reveal from acoustic field observations that the zooplankton community is undergoing diel vertical migration (DVM) behavior. Furthermore, using electroretinogram (ERG) recording under constant darkness, we show that the main migratory species, Arctic krill (Thysanoessa inermis) show endogenous increases in visual sensitivity during the subjective night. This change in sensitivity is comparable to that under exogenous dim light acclimations, although differences in speed of vision suggest separate mechanisms. We conclude that the extremely weak midday twilight experienced by krill at high latitudes during the darkest parts of the year has physiological and ecological relevance.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001413

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Abstract

A paradigm shift in the human chronotoxicity of xenobiotics would study two-sided desynchronized phenomena of interfacial interactions between cyclic or periodic environmental insults and the endogenous response and recovery profile. These systems-based networks are under the influence of well-synchronized biological clocks and their metabolic regulators. This perspective argues in favor of addressing the concept of synchronization in studies involving critical life windows of susceptibility, or circadian rhythms, or 24-hour (periodic) diurnal rhythms and answering whether these disruptions in synchronization would affect response and recovery or disease phenotypes associated with environmental insults, e.g., xenobiotics. Synchronization or synchrony is defined as the totality of elements that appear during the same time period within a system, including the network of interactions between the system’s elements. Desynchronized interfaces during critical life windows or in time-repeated exposure events would likely lead to initiating a cascade of adverse health effects associated with differentiated disease phenotypes.

https://onlinelibrary.wiley.com/doi/10.1002/bies.202100159

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Abstract

Objective: Emerging evidence shows that evening chronotype is associated with mental health problems, especially mood disorders, but few studies have investigated its association with schizophrenia. Based on meta-analytic methods, we aimed to test whether eveningness is greater in individuals with schizophrenia compared with healthy controls and patients with bipolar I disorder.

Method: Medline/Pubmed, Google Scholar, and EBSCO databases were searched up to April 2021 for articles investigating chronotype in individuals with schizophrenia. Two meta-analyses were conducted: individuals with schizophrenia compared with healthy controls and individuals with bipolar I disorder. These meta-analyses were followed by a meta-regression controlling for potential confounders.

Results: Five studies comprising 386 individuals with schizophrenia (age 32.73 years; 67.4% male), 320 with bipolar I disorder (age 31.26 years; 38.3% male) and 638 healthy controls (age 32.19 years; 50.6% male) were included. Participants with schizophrenia were moderately higher on eveningness than healthy controls but they did not differ from those with bipolar I disorder. The difference was not affected by gender, age, and the type of scale used for assessing chronotype.

Conclusions: Individuals with schizophrenia are more evening oriented than healthy controls and have a similar chronotype to those with bipolar I disorder. The results supported the hypothesis that evening chronotype might be a marker of, or a risk factor for, mental health problems in general and not just limited to affective disorders.

https://pubmed.ncbi.nlm.nih.gov/34332427/

Copyright © 2021 Elsevier B.V. All rights reserved

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Abstract

Melanopsin retinal ganglion cells (mRGCs) are the third class of retinal photoreceptors with unique anatomical, electrophysiological, and biological features. There are different mRGC subtypes with differential projections to the brain. These cells contribute to many nonimage-forming functions of the eye, the most relevant being the photoentrainment of circadian rhythms through the projections to the suprachiasmatic nucleus of the hypothalamus.

Other relevant biological functions include the regulation of the pupillary light reflex, mood, alertness, and sleep, as well as a possible role in formed vision.

The relevance of the mRGC-related pathways in the brain is highlighted by the role that the dysfunction and/or loss of these cells may play in affecting circadian rhythms and sleep in many neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s disease and in aging. Moreover, the occurrence of circadian dysfunction is a known risk factor for dementia.

In this chapter, the anatomy, physiology, and functions of these cells as well as their resistance to neurodegeneration in mitochondrial optic neuropathies or their predilection to be lost in other neurodegenerative disorders will be discussed.

https://www.sciencedirect.com/science/article/pii/B9780128199756000200?via%3Dihub

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Abstract

The night has historically been neglected in both disciplinary and interdisciplinary research. To some extent, this is not surprising, given the diurnal bias of human researchers and the difficulty of performing work at night. The night is, however, a critical element of biological, chemical, physical, and social systems on Earth. Moreover, research into social issues such as inequality, demographic changes, and the transition to a sustainable economy will be compromised if the night is not considered. Recent years, however, have seen a surge in research into the night. We argue that “night studies” is on the cusp of coming into its own as an interdisciplinary field, and that when it does, the field will consider questions that disciplinary researchers have not yet thought to ask.

Extract only, full study available at https://www.mdpi.com/2571-8800/3/1/1/htm

The challenges facing our planet and humanity during this century often have direct and indirect connections to the night that must not be overlooked. There is, therefore, a pressing need for interdisciplinary research into the night to come of age, expanding into a recognized field, because the night matters.

A pressing “nighttime” problem, for example, is growing concern over mismatches between social and biological time in humans. The 2017 Nobel Prize in Physiology and Medicine was awarded for the discovery of the molecular mechanisms in nearly all living organisms that govern circadian rhythms, ranging from activity patterns to blood pressure. The timing of many common human behaviors is often no longer aligned with these biological clocks, and there is ample concern that widespread insufficient or ineffective sleep [6] is detrimental to health. Sleep, however, is not simply a medical issue that can be isolated from broader social, cultural, and economic change. There are complex causes of changes in human sleep patterns over the past 150 years [7]. The development and expansion of artificial light at night has played a central role, with most cities now brightly illuminated [8,9]. Beyond lighting, factors such as incessant processes in industrial plants, connectivity across time zones, provision of 24/7 services including energy, security, and health care, and the possibility of constant technological connectivity in both professional and personal domains have expanded many human activities beyond previous temporal limits (e.g., [10]).Extending the hours of labor for non-essential services, to take but one example, both reflects and reinforces industrial capitalism [11]. Nighttime shifts that enable factories to raise profits for shareholders often pay more than equivalent day shifts. This financial incentive, in turn, often attracts workers who are economically marginal including many women, people of color, and immigrants. Despite increased compensation, the nighttime economy may end up worsening social and economic inequality and magnifying environmental injustice, for instance, if these groups end up suffering from higher rates of disease and poorer health. There are also social costs due to incongruities between the schedule of workers and those of their families. One may question whether night economies really raise local revenue, once sleep deficits and the healthcare costs of night shift workers are also considered. This example demonstrates how night is an “interdisciplinary object”; physical and social processes at night—circadian rhythms, capitalism, education, race, gender, security, mobility, public lighting, and inequality—are entangled in complex and sometimes unexpected ways.

Failing to consider the full interdisciplinary context of night has already affected real-world situations. Consider the recent replacement of outdoor lighting in Rome in 2017 [13]. The city’s lighting transition was undertaken within the frame of energy consumption and cost, and resulted in the replacement of existing warm color lamps with “colder” white LED lighting. Missing from consideration in the policy decision were public expectations and the cultural meaning of urban light, as well as the negative environmental side effects of broad spectrum (white) light [13]. As a result, residents and tourists had strong negative reactions to the light, arguing that the ancient city should not be lit with cold, harsh white lighting [14]. In addition, in trying to address one environmental problem (climate change), Rome may have worsened another (light pollution) in the process.

3. Conclusions

The night has experienced major changes in recent decades, and the pace of change is unlikely to slow down. While research into the night has expanded greatly in recent years, we believe that further networking and institutionalization is urgently needed. In order to develop into a recognized interdisciplinary field, night studies will need to see the establishment of journals, conference series, dedicated funding lines, research institutes, and university departments offering programs of study. If the field develops as we hope it will, perhaps it may eventually become recognized by the Greek term “nyctology”: the study of night matters.

4. Addendum

Note that another opinion on the “science of the night” with a different focus was recently published by Michele Acuto [20]. We agree strongly with Michele Acuto, and encourage readers to also read his piece. This manuscript was drafted independently over a period of in-person and online meetings spanning from 2017–2019, without any correspondence with Michele Acuto. https://www.mdpi.com/2571-8800/3/1/1/htm

We need a science of the night

Understanding what happens in cities after sunset is crucial to global sustainable development, argues Michele Acuto.

https://www.nature.com/articles/d41586-019-03836-2

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Abstract

The molecular circadian clock and symbiotic host-microbe relationships both evolved as mechanisms that enhance metabolic responses to environmental challenges. The gut microbiome benefits the host by breaking down diet-derived nutrients indigestible by the host and generating microbiota-derived metabolites that support host metabolism. Similarly, cellular circadian clocks optimize organismal physiology to the environment by influencing the timing and coordination of metabolic processes. Host-microbe interactions are influenced by dietary quality and timing, as well as daily light/dark cycles that entrain circadian rhythms in the host. Together, the gut microbiome and the molecular circadian clock play a coordinated role in neural processing, metabolism, adipogenesis, inflammation, and disease initiation and progression. This review examines the bidirectional interactions between the circadian clock, gut microbiota, and host metabolic systems and their effects on obesity and energy homeostasis. Directions for future research and the development of therapies that leverage these systems to address metabolic disease are highlighted.

Extract:

Our findings support the hypothesis that poor host metabolic outcomes are the result of asynchronous feeding signals, out of coordination with the light entrained circadian clock-driven anticipatory mechanisms regulating nutrient absorption and utilization, which may indirectly affect GM composition throughout the day. Small, achievable changes in behavior (e.g., changing timing of macronutrient consumption and improved sleep hygiene) that modulate GM signaling may harness innate biology to overcome the obesogenic environment that imposes a potential detriment to human health.

Publication History

Published online: March 30, 2021

Identification

DOI: https://doi.org/10.1016/j.cmet.2021.03.015

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Abstract

The circadian clock exerts significance influence on the immune system and disruption of circadian rhythms has been linked to inflammatory pathologies. Shift workers often experience circadian misalignment as their irregular work schedules disrupt the natural light-dark cycle, which in turn can cause serious health problems associated with alterations in genetic expressions of clock genes. In particular, shift work is associated with impairment in immune function, and those alterations are sex-specific. The goal of this study is to better understand the mechanisms that explain the weakened immune system in shift workers. To achieve that goal, we have constructed a mathematical model of the mammalian pulmonary circadian clock coupled to an acute inflammation model in the male and female rats. Shift work was simulated by an 8h-phase advance of the circadian system with sex-specific modulation of clock genes. The model reproduces the clock gene expression in the lung and the immune response to various doses of lipopolysaccharide (LPS). Under normal conditions, our model predicts that a host is more sensitive to LPS at circadian time (CT) CT12 versus CT0 due to a dynamic change of Interleukin 10 (IL-10), an anti-inflammatory cytokine. We identify REV-ERB as a key modulator of IL-10 activity throughout the circadian day. The model also predicts a reversal of the times of lowest and highest sensitivity to LPS, with males and females exhibiting an exaggerated response to LPS at CT0, which is countered by a blunted immune response at CT12. Overall, females produce fewer pro-inflammatory cytokines than males, but the extent of sequelae experienced by males and females varies across the circadian day. This model can serve as an essential component in an integrative model that will yield mechanistic understanding of how shift work-mediated circadian disruptions affect the inflammatory and other physiological responses.

Author summary

Shift work has a negative impact on health and can lead to chronic diseases and illnesses. Under regular work schedules, rest is a night time activity and work a daytime activity. Shift work relies on irregular work schedules which disrupt the natural sleep-wake cycle. This can in turn disrupt our biological clock, called the circadian clock, a network of molecular interactions generating biochemical oscillations with a near 24-hour period. Clock genes regulate cytokines before and during infection and immune agents can also impact the clock function. We provide a mathematical model of the circadian clock in the rat lung coupled to an acute inflammation model to study how the disruptive effect of shift work manifests itself in males and females during inflammation. Our results show that the extent of sequelae experienced by male and female rats depends on the time of infection. The goal of this study is to provide a mechanistic insight of the dynamics involved in the interplay between these two systems.

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Abstract

The circadian system, that is ubiquitous across species, generates ∼24 h rhythms in virtually all biological processes, and allows them to anticipate and adapt to the 24 h day/night cycle, thus ensuring optimal physiological function. Epidemiological studies show time-of-day variations in adverse cardiovascular (CV) events, and controlled laboratory studies demonstrate a circadian influence on key markers of CV function and risk. Furthermore, circadian misalignment, that is typically experienced by shift workers as well as by individuals who experience late eating, (social) jet lag, or circadian rhythm sleep-wake disturbances, increases CV risk factors. Therefore, understanding the mechanisms by which the circadian system regulates CV function, and which of these are affected by circadian disruption, may help to develop intervention strategies to mitigate CV risk.

https://pubmed.ncbi.nlm.nih.gov/31427142/

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Miguel Meira eCruz, Masaaki Miyazawa, David Gozal

European Respiratory Journal Jan 2020, 2001023; 

DOI: 10.1183/13993003.01023-2020

Circadian deregulation and poor or insufficient sleep may facilitate COVID19 infection and severity

SARS coronavirus 2 (SARS-CoV-2), the etiologic agent of the pandemic coronavirus disease 2019 (COVID-19), is a newly found member of the Coronaviridae family, and is closely related to, albeit with important differences from, the severe acute respiratory syndrome coronavirus (SARS-CoV) [1]. It enters human cells through the binding of surface spike (S) glycoprotein with angiotensin converting enzyme 2 (ACE2) [2–4]. The distal S1 subunit of the S protein is responsible for receptor binding while the transmembrane S2 subunit mediates fusion between viral envelope and target cell membrane following proteolytic cleavage by specific cellular enzymes such as serine protease TMPRSS2 for S protein priming [5]. As expression levels of ACE2 likely affect the efficiency of virus attachment and entry as well as disease severity [6], and the interactions between viral S protein and ACE2 may directly cause lung injury [7], ACE2 can be a potential target of therapeutic and preventative interventions [8].

Extract

Sleep and SARS-Cov 2 infection

Sleep, a circadian behavioral manifestation of major regulatory homeostatic mechanisms such as those associated with immunity, has also been shown to interact with host defenses at the molecular and cellular levels. Indeed, extensive literature has indicated the important role of homeostatic sleep in innate and adaptive immunity [46]. Furthermore, there are clear reciprocal dependencies between sleep duration and quality and the immune responses against viral, bacterial, and parasitic pathogens, the latter altering in turn sleep patterns [46]. Thus, it is likely that improved sleep quality and duration in the population may mitigate the propagation and severity of disease induced by SASRS-Cov-2 infection. Interestingly and potentially relevant to the SARS-Cov-2-ACE2 pathophysiological interdependency, Carhan et al. observed in a drosophila model that adult flies lacking ACER (an ACE2 homologue in Drosophila melanogaster) or those treated with peptidase inhibitors experienced disrupted night-time sleep [47]. We are unaware of any specific studies examining the effects of sleep on SARS-Cov-2 infection. Nonetheless, we should remark that coronaviruses are found with increased frequency in the tonsillar tissues of children suffering from obstructive sleep apnea [48].

In summary, the unique potential links between SARS-Cov-2 and circadian rhythms and sleep have been reviewed, and suggest the possibility that both of these homeostatic processes may significantly modify the susceptibility to infection as well as the overall clinical manifestation of the disease. Therefore, implementation of healthy sleep measures as a protective strategy against infection, and early detection of patients at risk for more severe disease (e.g., night-shift workers or patients with OSA) may enable improved implementation of supportive measures and lead to better outcomes.

https://erj.ersjournals.com/content/early/2020/04/27/13993003.01023-2020#sec-6

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