Journal Of Biological Rhythms[JOURNAL]
Sun
200 papers
Deciphering a Beetle Clock: Individual and Sex-Dependent Variation in Daily Activity Patterns.
R R, Prüser T, Schulz NKE … +4 more , Mayer PMF, Ogueta M, Stanewsky R, Kurtz J
J Biol Rhythms · 2024 Oct · PMID 39082472 · Full text
Circadian clocks are inherent to most organisms, including cryptozoic animals that seldom encounter direct light, and regulate their daily activity cycles. A conserved suite of clock genes underpins these rhythms. In thi...
Circadian clocks are inherent to most organisms, including cryptozoic animals that seldom encounter direct light, and regulate their daily activity cycles. A conserved suite of clock genes underpins these rhythms. In this study, we explore the circadian behaviors of the red flour beetle , a significant pest impacting stored grain globally. We report on how daily light and temperature cues synchronize distinct activity patterns in these beetles, characterized by reduced morning activity and increased evening activity, anticipating the respective environmental transitions. Although less robust, rhythmicity in locomotor activity is maintained in constant dark and constant light conditions. Notably, we observed more robust rhythmic behaviors in males than females with individual variation exceeding those previously reported for other insect species. RNA interference targeting the gene weakened locomotor activity rhythms. Our findings demonstrate the existence of a circadian clock and of clock-controlled behaviors in . Furthermore, they highlight substantial individual differences in circadian activity, laying the groundwork for future research on the relevance of individual variation in circadian rhythms in an ecological and evolutionary context.
A Detailed Re-Examination of the Gene Rescue Experiments Shows That Four to Six Cryptochrome-Positive Posterior Dorsal Clock Neurons (DN) of Can Control Morning and Evening Activity.
Sekiguchi M, Reinhard N, Fukuda A … +4 more , Katoh S, Rieger D, Helfrich-Förster C, Yoshii T
J Biol Rhythms · 2024 Oct · PMID 39082442 · Publisher ↗
Animal circadian clocks play a crucial role in regulating behavioral adaptations to daily environmental changes. The fruit fly exhibits 2 prominent peaks of activity in the morning and evening, known as morning (M) and...
Animal circadian clocks play a crucial role in regulating behavioral adaptations to daily environmental changes. The fruit fly exhibits 2 prominent peaks of activity in the morning and evening, known as morning (M) and evening (E) peaks. These peaks are controlled by 2 distinct circadian oscillators located in separate groups of clock neurons in the brain. To investigate the clock neurons responsible for the M and E peaks, a cell-specific gene expression system, the GAL4-UAS system, has been commonly employed. In this study, we re-examined the two-oscillator model for the M and E peaks of by utilizing more than 50 Gal4 lines in conjunction with the line, which enables the restoration of the clock function in specific cells in the () null mutant background. Previous studies have indicated that the group of small ventrolateral neurons (s-LN) is responsible for controlling the M peak, while the other group, consisting of the 5 ventrolateral neuron (5 LN) and the three cryptochrome (CRY)-positive dorsolateral neurons (LN), is responsible for the E peak. Furthermore, the group of posterior dorsal neurons 1 (DN) is thought to also contain M and E oscillators. In this study, we found that Gal4 lines directed at the same clock neuron groups can lead to different results, underscoring the fact that activity patterns are influenced by many factors. Nevertheless, we were able to confirm previous findings that the entire network of circadian clock neurons controls M and E peaks, with the lateral neurons playing a dominant role. In addition, we demonstrate that 4 to 6 CRY-positive DN cells are sufficient to generate M and E peaks in light-dark cycles and complex free-running rhythms in constant darkness. Ultimately, our detailed screening could serve as a catalog to choose the best Gal4 lines that can be used to rescue in specific clock neurons.
Toward an Indoor Lighting Solution for Social Jet Lag.
Neitz A, Rice A, Casiraghi L … +6 more , Bussi IL, Buhr ED, Neitz M, Neitz J, de la Iglesia HO, Kuchenbecker JA
J Biol Rhythms · 2024 Oct · PMID 39082441 · Full text
There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focus...
There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focused on stimulating the intrinsic photopigment, melanopsin; however, specialized color vision circuits have been elucidated in the primate retina that transmit blue-yellow cone-opponent signals to ipRGCs. We designed a light that stimulates color-opponent inputs to ipRGCs by temporally alternating short- and long-wavelength components that strongly modulate short-wavelength sensitive (S) cones. Two-hour exposure to this S-cone modulating light produced an average circadian phase advance of 1 h and 20 min in 6 subjects (mean age = 30 years) compared to no phase advance for the subjects after exposure to a 500 lux white light equated for melanopsin effectiveness. These results are promising for developing artificial lighting that is highly effective in controlling circadian rhythms by invisibly modulating cone-opponent circuits.
The Estrous Cycle Coordinates the Circadian Rhythm of Eating Behavior in Mice.
Alvord VM, Pendergast JS
J Biol Rhythms · 2024 Oct · PMID 39082411 · Full text
The estrous cycle regulates rhythms of locomotor activity, body temperature, and circadian gene expression. In female mice, activity increases on the night of proestrus, when elevated estrogens cause ovulation. Exogenous...
The estrous cycle regulates rhythms of locomotor activity, body temperature, and circadian gene expression. In female mice, activity increases on the night of proestrus, when elevated estrogens cause ovulation. Exogenous estradiol regulates eating behavior rhythms in female mice fed a high-fat diet, but it is unknown whether endogenous estrogens regulate eating rhythms. In this study, we investigated whether diurnal and circadian eating behavior rhythms change systematically across the estrous cycle. We first studied diurnal eating behavior rhythms in female C57BL/6J mice in 12L:12D. Estrous cycle stages were determined by vaginal cytology while eating behavior and wheel revolutions were continuously measured. The mice had regular 4- to 5-day estrous cycles. Consistent with prior studies, the greatest number of wheel revolutions occurred on the night of proestrus into estrus when systemic levels of estrogens peak. The amplitude, or robustness, of the eating behavior rhythm also fluctuated with 4- to 5-day cycles and peaked primarily during proestrus or estrus. The phases of eating behavior rhythms fluctuated, but not at 4- or 5-day intervals, and phases did not correlate with estrous cycle stages. After ovariectomy, the eating behavior rhythm amplitude fluctuated at irregular intervals. In constant darkness, the amplitude of the circadian eating behavior rhythm peaked every 4 or 5 days and coincided with the circadian day that had the greatest number of wheel revolutions, a marker of proestrus. These data suggest that fluctuations of ovarian hormones across the estrous cycle temporally organize the robustness of circadian eating behavior rhythms so that it peaks during ovulation and sexual receptivity.
Overlapping Central Clock Network Circuitry Regulates Circadian Feeding and Activity Rhythms in Drosophila.
Saurabh S, Meier RJ, Pireva LM … +2 more , Mirza RA, Cavanaugh DJ
J Biol Rhythms · 2024 Oct · PMID 39066485 · Publisher ↗
The circadian system coordinates multiple behavioral outputs to ensure proper temporal organization. Timing information underlying circadian regulation of behavior depends on a molecular circadian clock that operates wit...
The circadian system coordinates multiple behavioral outputs to ensure proper temporal organization. Timing information underlying circadian regulation of behavior depends on a molecular circadian clock that operates within clock neurons in the brain. In and other organisms, clock neurons can be divided into several molecularly and functionally discrete subpopulations that form an interconnected central clock network. It is unknown how circadian signals are coherently generated by the clock network and transmitted across output circuits that connect clock cells to downstream neurons that regulate behavior. Here, we have exhaustively investigated the contribution of clock neuron subsets to the control of two prominent behavioral outputs in : locomotor activity and feeding. We have used cell-specific manipulations to eliminate molecular clock function or induce electrical silencing either broadly throughout the clock network or in specific subpopulations. We find that clock cell manipulations produce similar changes in locomotor activity and feeding, suggesting that overlapping central clock circuitry regulates these distinct behavioral outputs. Interestingly, the magnitude and nature of the effects depend on the clock subset targeted. Lateral clock neuron manipulations profoundly degrade the rhythmicity of feeding and activity. In contrast, dorsal clock neuron manipulations only subtly affect rhythmicity but produce pronounced changes in the distribution of activity and feeding across the day. These experiments expand our knowledge of clock regulation of activity rhythms and offer the first extensive characterization of central clock control of feeding rhythms. Despite similar effects of central clock cell disruptions on activity and feeding, we find that manipulations that prevent functional signaling in an identified output circuit preferentially degrade locomotor activity rhythms, leaving feeding rhythms relatively intact. This demonstrates that activity and feeding are indeed dissociable behaviors, and furthermore suggests that differential circadian control of these behaviors diverges in output circuits downstream of the clock network.
Biological Sex Influences Daily Locomotor Rhythms in Mice Held Under Different Housing Conditions.
Pastrick A, Diaz M, Adaya G … +4 more , Montinola V, Arzbecker M, Joye DAM, Evans JA
J Biol Rhythms · 2024 Aug · PMID 38845380 · Full text
Daily rhythms are programmed by a central circadian clock that is modulated by photoperiod. Here, we recorded locomotor activity rhythms in C57Bl/6 or mPer2 mice of both sexes held under different housing conditions. Fir...
Daily rhythms are programmed by a central circadian clock that is modulated by photoperiod. Here, we recorded locomotor activity rhythms in C57Bl/6 or mPer2 mice of both sexes held under different housing conditions. First, we confirm that the structure of locomotor activity rhythms differs between male and female mice in both genetic backgrounds. Male mice exhibit a nightly "siesta," whereas female mice fluctuate between nights with and without a nightly siesta, which corresponds with changes in locomotor activity levels, circadian period, and vaginal cytology. The nightly siesta is modulated by the presence of a running wheel in both sexes but is not required for the infradian patterning of locomotor rhythms in females. Finally, photoperiodic changes in locomotor rhythms differed by sex, and females displayed phase-jumping responses earlier than males under a parametric photoentrainment assay simulating increasing day length. Collectively, these results highlight that sex and sex hormones influence daily locomotor rhythms under a variety of different environmental conditions.
Using Wearable Skin Temperature Data to Advance Tracking and Characterization of the Menstrual Cycle in a Real-World Setting.
Gombert-Labedens M, Alzueta E, Perez-Amparan E … +10 more , Yuksel D, Kiss O, de Zambotti M, Simon K, Zhang J, Shuster A, Morehouse A, Alessandro Pena A, Mednick S, Baker FC
J Biol Rhythms · 2024 Aug · PMID 38767963 · Full text
The menstrual cycle is a loop involving the interplay of different organs and hormones, with the capacity to impact numerous physiological processes, including body temperature and heart rate, which in turn display menst...
The menstrual cycle is a loop involving the interplay of different organs and hormones, with the capacity to impact numerous physiological processes, including body temperature and heart rate, which in turn display menstrual rhythms. The advent of wearable devices that can continuously track physiological data opens the possibility of using these prolonged time series of skin temperature data to noninvasively detect the temperature variations that occur in ovulatory menstrual cycles. Here, we show that the menstrual skin temperature variation is better represented by a model of oscillation, the cosinor, than by a biphasic square wave model. We describe how applying a cosinor model to a menstrual cycle of distal skin temperature data can be used to assess whether the data oscillate or not, and in cases of oscillation, rhythm metrics for the cycle, including mesor, amplitude, and acrophase, can be obtained. We apply the method to wearable temperature data collected at a minute resolution each day from 120 female individuals over a menstrual cycle to illustrate how the method can be used to derive and present menstrual cycle characteristics, which can be used in other analyses examining indicators of female health. The cosinor method, frequently used in circadian rhythms studies, can be employed in research to facilitate the assessment of menstrual cycle effects on physiological parameters, and in clinical settings to use the characteristics of the menstrual cycles as health markers or to facilitate menstrual chronotherapy.
The Free-Running Circasemilunar Period Is Determined by Counting Circadian Clock Cycles in the Marine Midge .
Neumann J, Rajendra D, Kaiser TS
J Biol Rhythms · 2024 Aug · PMID 38764210 · Full text
Semilunar rhythms are found in numerous marine organisms, but the molecular mechanism and functional principles of endogenous circasemilunar clocks remain elusive. Here, we explore the connection between the free-running...
Semilunar rhythms are found in numerous marine organisms, but the molecular mechanism and functional principles of endogenous circasemilunar clocks remain elusive. Here, we explore the connection between the free-running circasemilunar clock and the circadian clock in the marine midge with three different chronobiological assays. First, we found that the free-running circasemilunar period of the adult emergence rhythm in changes linearly with diel T-cycle length, supporting a day-counting mechanism. Second, under LD 6:6, periods of circasemilunar and circadian emergence were comparable to those under LD 12:12, indicating that the circasemilunar counter in relies on endogenous circadian oscillations rather than external T-cycles. Finally, when desynchronizing the circadian clock with constant light, the free-running circasemilunar emergence rhythm disappeared as well, suggesting that it requires a synchronized circadian clock. These results oppose the long-held view that free-running circasemilunar clock operates independently of the circadian clock. In a broader evolutionary context, our results strengthen the idea that the circasemilunar clocks of dipterous insects are based on different functional principles compared to the circasemilunar or circalunar clocks of marine annelids and algae. These divergent clock principles may indicate multiple evolutionary origins of circasemilunar and circalunar clocks.
Functional Analyses of Four Cryptochromes From Aquatic Organisms After Heterologous Expression in Circadian Clock Cells.
Chen C, Tamai TK, Xu M … +4 more , Petrone L, Oliveri P, Whitmore D, Stanewsky R
J Biol Rhythms · 2024 Aug · PMID 38544471 · Full text
Cryptochromes (Crys) represent a multi-facetted class of proteins closely associated with circadian clocks. They have been shown to function as photoreceptors but also to fulfill light-independent roles as transcriptiona...
Cryptochromes (Crys) represent a multi-facetted class of proteins closely associated with circadian clocks. They have been shown to function as photoreceptors but also to fulfill light-independent roles as transcriptional repressors within the negative feedback loop of the circadian clock. In addition, there is evidence for Crys being involved in light-dependent magneto-sensing, and regulation of neuronal activity in insects, adding to the functional diversity of this cryptic protein class. In mammals, Crys are essential components of the circadian clock, but their role in other vertebrates is less clear. In invertebrates, Crys can function as circadian photoreceptors, or as components of the circadian clock, while in some species, both light-receptive and clock factor roles coexist. In the current study, we investigate the function of Cry proteins in zebrafish (), a freshwater teleost expressing 6 genes. Zebrafish peripheral circadian clocks are intrinsically light-sensitive, suggesting the involvement of Cry in light-resetting. Echinoderms () represent the only class of deuterostomes that possess an orthologue () of the light-sensitive Cry, which is an important component of the light-resetting pathway, but also works as transcriptional repressor in peripheral clocks of fruit flies. We therefore investigated the potential of different zebrafish genes and to replace the light-resetting and repressor functions of Cry by expressing them in fruit flies lacking endogenous function. Using various behavioral and molecular approaches, we show that most Cry proteins analyzed are able to fulfill circadian repressor functions in flies, except for one of the zebrafish Crys, encoded by . Cry4a also shows a tendency to support light-dependent Cry functions, indicating that it might act in the light-input pathway of zebrafish.
Divergent Circadian Foraging Strategies in Response to Diurnal Predation Versus Persistent Rain in Asian Weaver Ant, , Suggest Possible Energetic Trade-offs.
Dolai A, Soltani S, Smarr B … +1 more , Das A
J Biol Rhythms · 2024 Jun · PMID 38459718 · Full text
The study of chronobiology of foraging behavior in social insects offers valuable models for the investigation of circadian rhythms. We scored hourly nest entries and exits of (Asian weaver ant) workers in 9 active non-...
The study of chronobiology of foraging behavior in social insects offers valuable models for the investigation of circadian rhythms. We scored hourly nest entries and exits of (Asian weaver ant) workers in 9 active non-polydomous nests on days with and without rain and with and without a primarily diurnal predator present. After determining that display a high nest fidelity, we focused exclusively on analyzing nest entry counts: we found a significant decrease in overall entry counts of individual ants on rainy days compared with non-rainy days ( < 0.0001). They usually maintain a typical diurnal pattern of foraging activity; however, that regularity was often distorted during rainy periods but appeared to quickly revert to typical patterns following rain. This lack of compensatory foraging activity following a period of rain supports the hypothesis that these ants have enough food reserves to withstand a pure masking-induced suppression of foraging activity. Predation through bird anting, too, decreased foraging activity but appeared to cause a reversal in foraging activity timing from diurnal to nocturnal foraging. Daily periodicity of foraging was significantly disrupted in most nests during rain; however, daily foraging periodicity was disrupted in only one nest due to presence of predators. Thus, rain and predation both exert significant impacts on the overall foraging activity of Asian weaver ants, but while persistent pressure from rain seemed to primarily cause masking (diminution) of circadian foraging activity, predation restricted to the daytime resulted in phase-inversion to nocturnal foraging activity, with little diminution. This is consistent with different energetic strategies being used in response to different pressures by this species.
Circadian Variation in the Response to Vaccination: A Systematic Review and Evidence Appraisal.
Wyse CA, Rudderham LM, Nordon EA … +3 more , Ince LM, Coogan AN, Lopez LM
J Biol Rhythms · 2024 Jun · PMID 38459699 · Full text
Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vacc...
Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vaccination might depend on the time of day of exposure. This study assessed whether the time of day of vaccination (TODV) is associated with the subsequent immune and clinical response by conducting a systematic review of previous studies. The Cochrane Library, PubMed, Google, Medline, and Embase were searched for studies that reported TODV and immune and clinical outcomes, yielding 3114 studies, 23 of which met the inclusion criteria. The global severe acute respiratory syndrome coronavirus 2 vaccination program facilitated investigation of TODV and almost half of the studies included reported data collected during the COVID-19 pandemic. There was considerable heterogeneity in the demography of participants and type of vaccine, and most studies were biased by failure to account for immune status prior to vaccination, self-selection of vaccination time, or confounding factors such as sleep, chronotype, and shiftwork. The optimum TODV was concluded to be afternoon (5 studies), morning (5 studies), morning and afternoon (1 study), midday (1 study), and morning or late afternoon (1 study), with the remaining 10 studies reporting no effect. Further research is required to understand the relationship between TODV and subsequent immune outcome and whether any clinical benefit outweighs the potential effect of this intervention on vaccine uptake.
Association Between Augmentation Index and Total Sleep Time in Night Shift Workers.
Gusmão WDP, Silva VM, Paiva AMG … +3 more , Mota-Gomes MA, Nadruz W, Moreno CRC
J Biol Rhythms · 2024 Apr · PMID 38433444 · Publisher ↗
Augmentation index and pulse wave velocity are markers of vascular compromise and independent predictors of cardiovascular risk and mortality. While the link between shift work and heightened cardiovascular risk is estab...
Augmentation index and pulse wave velocity are markers of vascular compromise and independent predictors of cardiovascular risk and mortality. While the link between shift work and heightened cardiovascular risk is established, the intricate genesis of early cardiovascular outcomes in shift workers remains incompletely understood. However, there is evidence that sleep duration plays a role in this regard. Here we evaluate the association of total sleep time with pulse wave velocity, augmentation index, and central blood pressure in night shift workers. This study cross-sectionally evaluated the association of total sleep time evaluated by 10-day monitoring actigraphy with augmentation index, pulse wave velocity, and brachial and central blood pressure evaluated by oscillometry in nursing professionals, 63 shift workers (89% women; age = 45.0 ± 10.5 years), and 17 (100% women; age = 41.8 ± 15.6) day workers. There were no differences in the studied variables between shift workers and day workers. Results of correlation analysis demonstrated that pulse wave velocity, central systolic blood pressure, central diastolic blood pressure, brachial systolic blood pressure, and brachial diastolic blood pressure tended to have significant correlation with each other, while these measures did not have a significant relationship with augmentation index in both groups. However, results of adjusted restricted cubic spline analysis showed a U-shaped-curve association between total sleep time and augmentation index ( < 0.001 for trend) with a nadir at 300-360 min of total sleep time in shift workers. The present study showed that total sleep time, assessed by actigraphy, had a U-shaped association with augmentation index in shift workers, which indicated better characteristics of vascular functionality when sleep time was 5-6 h in the workers studied.
Using Polygenic Scores for Circadian Rhythms to Predict Wellbeing, Depressive Symptoms, Chronotype, and Health.
Landvreugd A, Pool R, Nivard MG … +1 more , Bartels M
J Biol Rhythms · 2024 Jun · PMID 38425306 · Full text
The association between circadian rhythms and diseases has been well established, while the association with mental health is less explored. Given the heritable nature of circadian rhythms, this study aimed to investigat...
The association between circadian rhythms and diseases has been well established, while the association with mental health is less explored. Given the heritable nature of circadian rhythms, this study aimed to investigate the relationship between genes underlying circadian rhythms and mental health outcomes, as well as a possible gene-environment correlation for circadian rhythms. Polygenic scores (PGSs) represent the genetic predisposition to develop a certain trait or disease. In a sample from the Netherlands Twin Register ( = 14,021), PGSs were calculated for two circadian rhythm measures: morningness and relative amplitude (RA). The PGSs were used to predict mental health outcomes such as subjective happiness, quality of life, and depressive symptoms. In addition, we performed the same prediction analysis in a within-family design in a subset of dizygotic twins. The PGS for morningness significantly predicted morningness ( = 1.55%) and depressive symptoms ( = 0.22%). The PGS for RA significantly predicted general health ( = 0.12%) and depressive symptoms ( = 0.20%). Item analysis of the depressive symptoms showed that 4 out of 14 items were significantly associated with the PGSs. Overall, the results showed that people with a genetic predisposition of being a morning person or with a high RA are likely to have fewer depressive symptoms. The four associated depressive symptoms described symptoms related to decision-making, energy, and feeling worthless or inferior, rather than sleep. Based on our findings future research should include a substantial role for circadian rhythms in depression research and should further explore the gene-environment correlation in circadian rhythms.
One Health: Circadian Medicine Benefits Both Non-human Animals and Humans Alike.
Farag HI, Murphy BA, Templeman JR … +9 more , Hanlon C, Joshua J, Koch TG, Niel L, Shoveller AK, Bedecarrats GY, Ellison A, Wilcockson D, Martino TA
J Biol Rhythms · 2024 Jun · PMID 38379166 · Full text
Circadian biology's impact on human physical health and its role in disease development and progression is widely recognized. The forefront of circadian rhythm research now focuses on translational applications to clinic...
Circadian biology's impact on human physical health and its role in disease development and progression is widely recognized. The forefront of circadian rhythm research now focuses on translational applications to clinical medicine, aiming to enhance disease diagnosis, prognosis, and treatment responses. However, the field of circadian medicine has predominantly concentrated on human healthcare, neglecting its potential for transformative applications in veterinary medicine, thereby overlooking opportunities to improve non-human animal health and welfare. This review consists of three main sections. The first section focuses on the translational potential of circadian medicine into current industry practices of agricultural animals, with a particular emphasis on horses, broiler chickens, and laying hens. The second section delves into the potential applications of circadian medicine in small animal veterinary care, primarily focusing on our companion animals, namely dogs and cats. The final section explores emerging frontiers in circadian medicine, encompassing aquaculture, veterinary hospital care, and non-human animal welfare and concludes with the integration of One Health principles. In summary, circadian medicine represents a highly promising field of medicine that holds the potential to significantly enhance the clinical care and overall health of all animals, extending its impact beyond human healthcare.
The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward.
Ono D, Weaver DR, Hastings MH … +3 more , Honma KI, Honma S, Silver R
J Biol Rhythms · 2024 Apr · PMID 38366616 · Full text
It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments in the field was published in the . Here, we explore n...
It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments in the field was published in the . Here, we explore new mechanisms and concepts that have emerged in the subsequent 25 years. Since 1997, methodological developments, such as luminescent and fluorescent reporter techniques, have revealed intricate relationships between cellular and network-level mechanisms. In particular, specific neuropeptides such as arginine vasopressin, vasoactive intestinal peptide, and gastrin-releasing peptide have been identified as key players in the synchronization of cellular circadian rhythms within the SCN. The discovery of multiple oscillators governing behavioral and physiological rhythms has significantly advanced our understanding of the circadian clock. The interaction between neurons and glial cells has been found to play a crucial role in regulating these circadian rhythms within the SCN. Furthermore, the properties of the SCN network vary across ontogenetic stages. The application of cell type-specific genetic manipulations has revealed components of the functional input-output system of the SCN and their correlation with physiological functions. This review concludes with the high-risk effort of identifying open questions and challenges that lie ahead.
Investigating the Roles for Essential Genes in the Regulation of the Circadian Clock in Using CRISPR Interference.
Boodaghian N, Park H, Cohen SE
J Biol Rhythms · 2024 Jun · PMID 38357890 · Publisher ↗
Circadian rhythms are found widely throughout nature where cyanobacteria are the simplest organisms, in which the molecular details of the clock have been elucidated. Circadian rhythmicity in cyanobacteria is carried out...
Circadian rhythms are found widely throughout nature where cyanobacteria are the simplest organisms, in which the molecular details of the clock have been elucidated. Circadian rhythmicity in cyanobacteria is carried out via the KaiA, KaiB, and KaiC core oscillator proteins that keep ~24 h time. A series of input and output proteins-CikA, SasA, and RpaA-regulate the clock by sensing environmental changes and timing rhythmic activities, including global rhythms of gene expression. Our previous work identified a novel set of KaiC-interacting proteins, some of which are encoded by genes that are essential for viability. To understand the relationship of these essential genes to the clock, we applied CRISPR interference (CRISPRi) which utilizes a deactivated Cas9 protein and single-guide RNA (sgRNA) to reduce the expression of target genes but not fully abolish their expression to allow for survival. Eight candidate genes were targeted, and strains were analyzed by quantitative real-time PCR (qRT-PCR) for reduction of gene expression, and rhythms of gene expression were monitored to analyze circadian phenotypes. Strains with reduced expression of SynPCC7942_0001, , which encodes for the β-clamp of the replicative DNA polymerase, or SynPCC7942_1081, which likely encodes for a KtrA homolog involved in K transport, displayed longer circadian rhythms of gene expression than the wild type. As neither of these proteins have been previously implicated in the circadian clock, these data suggest that diverse cellular processes, DNA replication and K transport, can influence the circadian clock and represent new avenues to understand clock function.
The Impact of Pupil Constriction on the Relationship Between Melanopic EDI and Melatonin Suppression in Young Adult Males.
Schöllhorn I, Stefani O, Lucas RJ … +3 more , Spitschan M, Epple C, Cajochen C
J Biol Rhythms · 2024 Jun · PMID 38348477 · Full text
The pupil modulates the amount of light that reaches the retina. Not only luminance but also the spectral distribution defines the pupil size. Previous research has identified steady-state pupil size and melatonin attenu...
The pupil modulates the amount of light that reaches the retina. Not only luminance but also the spectral distribution defines the pupil size. Previous research has identified steady-state pupil size and melatonin attenuation to be predominantly driven by melanopsin, which is expressed by a unique subgroup of intrinsically photosensitive retinal ganglion cells (ipRGCs) that are sensitive to short-wavelength light (~480 nm). Here, we aimed to selectively target the melanopsin system during the evening, while measuring steady-state pupil size and melatonin concentrations under commonly experienced evening light levels (<90 lx). Therefore, we used a five-primary display prototype to generate light conditions that were matched in terms of L-, M-, and S-cone-opic irradiances, but with high and low melanopic irradiances (~3-fold difference). Seventy-two healthy, male participants completed a 2-week study protocol. The volunteers were assigned to one of the four groups that differed in luminance levels (27-285 cd/m). Within the four groups, each volunteer was exposed to a low melanopic (LM) and a high melanopic (HM) condition. The two 17-h study protocols comprised 3.5 h of light exposure starting 4 h before habitual bedtime. Median pupil size was significantly smaller during HM than LM in all four light intensity groups. In addition, we observed a significant correlation between melanopic weighted corneal illuminance (melanopic equivalent daylight illuminance [mEDI]) and pupil size, such that higher mEDI values were associated with smaller pupil size. Using pupil size to estimate retinal irradiance showed a qualitatively similar goodness of fit as mEDI for predicting melatonin suppression. Based on our results here, it remains appropriate to use melanopic irradiance measured at eye level when comparing light-dependent effects on evening melatonin concentrations in healthy young people at rather low light levels.
Mathematical Analysis of Light-sensitivity Related Challenges in Assessment of the Intrinsic Period of the Human Circadian Pacemaker.
Usmani IM, Dijk DJ, Skeldon AC
J Biol Rhythms · 2024 Apr · PMID 38317600 · Full text
Accurate assessment of the intrinsic period of the human circadian pacemaker is essential for a quantitative understanding of how our circadian rhythms are synchronized to exposure to natural and man-made light-dark (LD)...
Accurate assessment of the intrinsic period of the human circadian pacemaker is essential for a quantitative understanding of how our circadian rhythms are synchronized to exposure to natural and man-made light-dark (LD) cycles. The gold standard method for assessing intrinsic period in humans is forced desynchrony (FD) which assumes that the confounding effect of lights-on assessment of intrinsic period is removed by scheduling sleep-wake and associated dim LD cycles to periods outside the range of entrainment of the circadian pacemaker. However, the observation that the mean period of free-running blind people is longer than the mean period of sighted people assessed by FD (24.50 0.17 h vs 24.15 0.20 h, 0.001) appears inconsistent with this assertion. Here, we present a mathematical analysis using a simple parametric model of the circadian pacemaker with a sinusoidal velocity response curve (VRC) describing the effect of light on the speed of the oscillator. The analysis shows that the shorter period in FD may be explained by exquisite sensitivity of the human circadian pacemaker to low light intensities and a VRC with a larger advance region than delay region. The main implication of this analysis, which generates new and testable predictions, is that current quantitative models for predicting how light exposure affects entrainment of the human circadian system may not accurately capture the effect of dim light. The mathematical analysis generates new predictions which can be tested in laboratory experiments. These findings have implications for managing healthy entrainment of human circadian clocks in societies with abundant access to light sources with powerful biological effects.
Circadian Rhythms in Skin Barrier Function in Atopic Dermatitis: A Pilot Study.
Iwanaszko M, Waldeck N, Anafi R … +3 more , Paller AS, Zee PC, Fishbein AB
J Biol Rhythms · 2024 Apr · PMID 38305093 · Full text
Atopic dermatitis (AD) is symptomatically worse in the evening, but the mechanism driving nocturnal eczema remains elusive. Our objective was to determine the circadian rhythm of skin barrier function measured by transep...
Atopic dermatitis (AD) is symptomatically worse in the evening, but the mechanism driving nocturnal eczema remains elusive. Our objective was to determine the circadian rhythm of skin barrier function measured by transepidermal water loss (TEWL) in AD patients and explore the molecular underpinnings. A pilot study was performed on a diverse group of AD ( = 4) and control ( = 2) young patients. We used an inpatient tightly controlled, modified, constant routine protocol. TEWL was measured at least every 90 min in the antecubital fossa (lesional) and forearm, while whole blood samples were collected every 4 h. Results show a significant difference in the antecubital fossa TEWL in the AD group versus controls. TEWL in control skin decreases starting a few hours prior to bedtime, both in the antecubital fossa and in the forearm, while in the AD forearm skin, pre-bedtime TEWL increases. We identified 1576 differentially expressed genes using a time-dependent model. The top 20 upregulated gene ontology pathways included neuronal pathways, while the downregulated functional terms included innate immune signaling and viral response. Similar pathways positively correlated with forearm TEWL in controls and inversely with the AD group. Upregulation in sensory perception pathways correlated with increases in lesional (antecubital fossa) TEWL in the evening. Results show skin barrier function worsens in the evening in the AD group, at a time when barrier is normally rejuvenating in healthy skin. This timing and the detection of transcriptomic signatures of sensory perception and diminished viral response might correspond to the nocturnal itch. Larger studies are needed to evaluate these associations in the skin.
Evaluating the Adaptive Fitness of Circadian Clocks and their Evolution.
Jabbur ML, Dani C, Spoelstra K … +2 more , Dodd AN, Johnson CH
J Biol Rhythms · 2024 Apr · PMID 38185853 · Full text
Surely most chronobiologists believe circadian clocks are an adaptation of organisms that enhances fitness, but are we certain that this focus of our research effort really confers a fitness advantage? What is the eviden...
Surely most chronobiologists believe circadian clocks are an adaptation of organisms that enhances fitness, but are we certain that this focus of our research effort really confers a fitness advantage? What is the evidence, and how do we evaluate it? What are the best criteria? These questions are the topic of this review. In addition, we will discuss selective pressures that might have led to the historical evolution of circadian systems while considering the intriguing question of whether the ongoing climate change is modulating these selective pressures so that the clock is still evolving.
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