Circadian Research Articles

Accurately predicting mood episodes in mood disorder patients using wearable sleep and circadian rhythm features

Accurately predicting mood episodes in mood disorder patients using wearable sleep and circadian rhythm features

Effect of Standard versus Advanced Dimmable Lighting Systems on the Circadian Rhythms of Hospital Personnel

Effect of Standard versus Advanced Dimmable Lighting Systems on the Circadian Rhythms of Hospital Personnel

Behavioural phenotypes of Dicer knockout in the mouse SCN

AbstractThe suprachiasmatic nucleus (SCN) is the master clock that directly dictates behavioural rhythms to anticipate the earth's light/dark cycles. Although post‐transcriptional regulators called microRNAs have been implicated in physiological SCN function, how the absence of the entire mature miRNome impacts SCN output has not yet been explored. To study the behavioural consequences of miRNA depletion in the SCN, we first generated a mouse model in which Dicer is inactivated in the SCN by crossing Syt10Cre mice with Dicerflox mice to study behavioural consequences of miRNA depletion in the SCN. Loss of all mature miRNAs in the SCN shortened the circadian period length by ~37 minutes at the tissue level and by ~45 minutes at the locomotor activity level. Moreover, knockout animals exhibited a reduction in the precision of the circadian rhythm with more variable activity onsets under both LD 12:12 and DD conditions. We also observed that knockouts with higher onset variations were inclined to develop ultradian rhythms under constant light. In a second mouse model, recombination of Dicerflox via Cre delivery specifically in the SCN resulted in loss of behavioural rhythms in some animals depending on the injection efficiency. Together, our observations highlight the importance of microRNAs for a physiological SCN function and their pivotal role in robust circadian oscillations.

Chrononutrition and Mental Health: Exploring Links Between Eating Patterns Circadian Rhythms and Psychological Well-being

This study investigates the relationship between chrononutrition—timing and patterns of food intake—and mental health, focusing on how circadian rhythms influence psychological well-being. Using a qualitative approach, this literature review synthesizes recent research exploring the connections between eating patterns, biological rhythms, and mental health outcomes, such as anxiety, depression, and overall mood stability. Findings indicate that irregular eating times, late-night meals, and skipping meals disrupt circadian alignment, potentially leading to mood dysregulation and decreased psychological resilience. Conversely, eating in sync with the body’s natural circadian rhythms appears to support mental health, with regular meal timing shown to enhance mood and reduce anxiety symptoms. The review also highlights the importance of specific nutrients in promoting stable circadian cycles, suggesting that diets rich in complex carbohydrates, proteins, and certain vitamins may aid in stabilizing mood. These findings underscore the need for an integrative approach to nutrition and mental health that considers both the timing and composition of meals. This review provides valuable insights into the emerging field of chrononutrition, emphasizing the potential of circadian-aligned eating as a preventive and therapeutic strategy for mental health. Further qualitative studies are recommended to explore individualized chrononutrition interventions and their effects on mental well-being across diverse populations.

Fine mapping and candidate gene mining of QSc/Sl.cib-7H for spike compactness and length and its pleiotropic effects on yield-related traits in barley (Hordeum vulgare L.).

A major locus for spike compactness and length was mapped on chromosome 7H and its pleiotropic effects, candidate genes and transcriptional regulatory network were analyzed. Spike compactness (SC) and length (SL) are important traits of barley (Hordeum vulgare L.) due to their close association with grain yield. In this study, a major SC and SL locus QSc/Sl.cib-7H was primarily identified on chromosome 7H by bulked segregant analysis, and further fine mapped to a recombination cold spot expanding 244.36-388.09Mb by developing a secondary population using residual heterozygous lines. This region is much more accurate than previously reported spike compactness loci on chromosome 7H.The strong effects of QSc/Sl.cib-7H on SL and SC were validated in two pair of near isogenic lines (NILs) and diverse genetic backgrounds. QSc/Sl.cib-7H exhibited pleiotropic effects on plant height (PH), thousand grain weight and grain length, and did not significantly influence the spikelet number of main spike (SMS) and grain width. Transcriptome analysis based on NILs showed that regulation of SC and SL might be related to the plant circadian rhythm pathway. The candidate genes were mined by analyzing variants and expression patterns of genes in the target region employing multiple genome and transcriptome data. This study takes a further step towards cloning of QSc/Sl.cib-7H, and the data obtained and the developed molecular markers will facilitate its utilization in barley breeding.

The early dodder gets the host: decoding the coiling patterns of Cuscuta campestris with automated image processing.

We developed an in-house Python-based image analysis pipeline to investigate the movement patterns of Cuscuta. Our analysis unveiled that the coiling and circumnutation movements of Cuscuta are regulated by its intrinsic circadian rhythm. Cuscuta spp., commonly known as dodders, are rootless and leafless stem parasitic plants. Upon germination, Cuscuta starts rotating immediately in a counterclockwise direction (circumnutation) to locate a host plant, creating a seamless vascular connection to steal water and nutrients from its host. In this study, our aim was to elucidate the dynamics of the coiling patterns of Cuscuta, which is an essential step for successful parasitism. Using time-lapse photography, we recorded the circumnutation and coiling movements of C. campestris at different inoculation times on non-living hosts. Subsequent image analyses were facilitated through an in-house Python-based image processing pipeline to detect coiling locations, angles, initiation and completion times, and duration of coiling stages in between. The study revealed that the coiling efficacy of C. campestris varied with the inoculation time of day, showing higher success and faster initiation in morning than in evening. These observations suggest that Cuscuta, despite lacking leaves and a developed chloroplast, can discern photoperiod changes, significantly determining its parasitic efficiency. The automated image analysis results confirmed the reliability of our Python pipeline by aligning closely with manual annotations. This study provides significant insights into the parasitic strategies of C. campestris and demonstrates the potential of integrating computational image analysis in plant biology for exploring complex plant behaviors. Furthermore, this method provides an efficient tool for investigating plant movement dynamics, laying the foundation for future studies on mitigating the economic impacts of parasitic plants.

In vivo functional significance of direct physical interaction between period and cryptochrome in mammalian circadian rhythm generation

Abstract In the current model, the auto-negative feedback action of Period (Per) and Cryptochrome (Cry) on their own transcription is the hallmark mechanism driving cell-autonomous circadian rhythms. Although this model likely makes sense even if Per and Cry undertake this action in a mutually independent manner, many studies have suggested the functional significance of direct physical interaction between Per and Cry. However, even though the interaction is a biochemical process that pertains to the fundamentals of the circadian oscillator, its in vivo contribution to circadian rhythm generation remains undefined. To answer this question, we focused on zinc coordination between Per and Cry, whose contribution to circadian rhythm generation remains undefined. Specifically, we aimed to impair endogenous Per-Cry association by introducing an amino acid substitution to zinc-coordinating residues located at the Per1 and Per2 C-terminal facing Cry in mice. These mice did not show severe impairment in the Per-Cry physical interaction, but rather a shortened period and decreased robustness in circadian rhythms at the tissue-autonomous and whole-body levels. Furthermore, these mice also showed a decreased in Per half-life, suggesting that impaired fine-tuning of Per half-life caused abnormal circadian period and robustness in vivo. We also found a minor but significant impact of a reindeer-specific Per2 mutation located in the Per-Cry interface on circadian rhythms in vivo. These lines of evidence indicate that only partial impairment of the Per-Cry physical interaction produces a substantial effect on circadian period and robustness, supporting the in vivo functional significance of the interaction.

Development of a revised version of the SCRAM questionnaire to evaluate sleep, circadian rhythms, and mood characteristics

ABSTRACT Sleep quality, chronotype, and mood may be closely interconnected processes. Typically, such constructs are measured independently, leaving out important information regarding their intrinsic relationships. The Sleep, Circadian Rhythms, and Mood (SCRAM) questionnaire is a promising tool for measuring sleep, chronotype, understood as diurnal preference, and depressive symptomatology, and the interrelationships between them. Anxiety has also been linked to sleep quality, chronotype, and depression, but there is currently no scale that measures these constructs together. This study aims to validate a revised version of the SCRAM questionnaire (rSCRAM), incorporating items to measure anxious mood. 486 Italian participants were involved in two studies. In Study 1, principal component analysis (PCA) identified representative anxiety elements from validated questionnaires. In Study 2, after adding the anxiety elements, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) established a 4-factor, 16-item model. The rSCRAM demonstrated excellent psychometric properties: high internal consistency (α = 0.72–0.90) and a strong test-retest reliability of the scales over 2 weeks (r = 0.73–0.82), a high correlation for convergent validity, and low correlations for divergent validity. The rSCRAM questionnaire measures the constructs for which it was created and revised. Including the anxiety scale enhances its utility in assessing mental health constructs within a single instrument.

Beyond the Scale: Exploring the Endocannabinoid System's Impact on Obesity.

This review explores the role of the endocannabinoid system (ECS) in regulating energy balance, food intake, and metabolism, with a focus on how ECS dysregulation contributes to obesity. The goal is to provide insights into the mechanisms underlying obesity and its associated metabolic disorders. Recent research indicates that the ECS significantly influences food intake, fat storage, insulin sensitivity, and inflammation, all of which are central to the development and progression of obesity. New research areas include the interaction between the ECS and gut microbiota, circadian rhythms of the ECS, and the impact of genetic and epigenetic factors on ECS function. Interest in the therapeutic potential of targeting the ECS has grown, with earlier treatments like CB1 receptor antagonists showing mixed results in efficacy and safety. Evidence from both animal and human studies highlight the impact of elevated levels of the endocannabinoids anandamide and 2-AG on food intake, insulin resistance, visceral fat accumulation, and metabolic disturbances associated with obesity. The review explores the interaction between the ECS and other physiological systems, including gut-brain communication, circadian rhythms, as well as leptin and ghrelin signaling. Additionally, genetic and epigenetic factors influencing ECS function are examined, emphasizing their contribution to obesity susceptibility. While therapeutic approaches targeting the ECS, particularly CB1 receptor antagonism, have shown potential in managing obesity, the review acknowledges the challenges posed by central nervous system side effects in earlier treatments like rimonabant. However, recent advancements in peripherally restricted CB1 antagonists offer renewed hope for safer and more effective obesity treatments. The review concludes by addressing future research directions and therapeutic strategies to combat this global health challenge.

Formulation, Development and Evaluation of Pulsatile Tablets of Etoricoxib

Aim: This research aimed to develop a pulsatile drug delivery system (PDDS) for etoricoxib, selective COX-2 inhibitor analgesic, to address the limitations of conventional formulations by releasing the drug at specific intervals aligned with the circadian rhythm of pain. Method: Core tablets containing Etoricoxib were prepared by direct compression with varied concentrations of croscarmellose sodium as a superdisintegrant. The optimized core tablets were coated using hydrophilic (HPMC K4M) and hydrophobic (ethyl cellulose) polymers in different ratios to create press-coated pulsatile tablets with varying lag times. Physical properties hardness, thickness, friability, and disintegration, drug content uniformity, and in vitro release were evaluated. Results: The core tablets exhibited rapid drug release, with batch C3 showing 98.61% release within 60 minutes. Press-coated formulations with different polymer ratios exhibited varying lag times, with batch F3 achieving the optimal balance—providing a 4-hour lag time and 96.6% drug release over 8 hours. Stability studies confirmed the physical and chemical stability of the optimized formulation (F3) over 6 months under accelerated conditions. Conclusion: The developed press-coated pulsatile tablets of etoricoxib successfully achieved a controlled lag time and sustained drug release profile, making them suitable for chronopharmacological management of pain. Keywords: Etoricoxib, Pulsatile Drug Delivery System, Chronopharmacology, Press-Coated Tablets. etc

Revealing the Bioactivities of Physalia physalis Venom Using Drosophila as a Model

Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila melanogaster. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications.

EARLY FLOWERING 3 alleles affect the temperature responsiveness of the circadian clock in Chinese cabbage.

Temperature is an environmental cue that entrains the circadian clock, adapting it to local thermal and photoperiodic conditions that characterize different geographic regions. Circadian clock thermal adaptation in leafy vegetables such as Chinese cabbage (Brassica rapa ssp. pekinensis) is poorly understood but essential to sustain and increase vegetable production under changing climates. We investigated circadian rhythmicity in natural Chinese cabbage accessions grown at 14, 20, and 28 °C. The circadian period was significantly shorter at 20 °C than at either 14 or 28 °C, and the responses to increasing temperature and temperature compensation (Q10) were associated with population structure. Genome-wide association studies mapping identified variation responsible for temperature compensation as measured by Q10 value for temperature increase from 20 to 28 °C. Haplotype analysis indicated that B. rapa EARLY FLOWERING 3 H1 Allele (BrELF3H1) conferred a significantly higher Q10 value at 20 to 28 °C than BrELF3H2. Co-segregation analyses of an F2 population derived from a BrELF3H1 × BrELF3H2 cross revealed that variation among BrELF3 alleles determined variation in the circadian period of Chinese cabbage at 20 °C. However, their differential impact on circadian oscillation was attenuated at 28 °C. Transgenic complementation in Arabidopsis thaliana elf3-8 mutants validated the involvement of BrELF3 in the circadian clock response to thermal cues, with BrELF3H1 conferring a higher Q10 value than BrELF3 H2 at 20 to 28 °C. Thus, BrELF3 is critical to the circadian clock response to ambient temperature in Chinese cabbage. These findings have clear implications for breeding new varieties with enhanced resilience to extreme temperatures.

Correlations of the Circadian Rhythmicity of Blood Pressure With Erectile Dysfunction.

Erectile dysfunction (ED) and cardiovascular diseases (CVD) share common pathophysiological mechanisms. This study aimed to assess the relationship between ED and its severity with the risk of developing CVD by analyzing changes in the circadian blood pressure (BP) rhythm. In the study, 24-h BP levels of 192 (94 with ED and 98 controls) participants with no history of CVD were evaluated using an ambulatory blood pressure monitoring (ABPM) device. The International Index of Erectile Function (IIEF) questionnaire was used to assess the ED severity in the study group. ABPM measurements revealed higher BP values among the ED group. The nondipper pattern was significantly more frequent in the ED group compared to the controls (56.2%vs. 77.1%, p<0.01). Blood pressure variability parameters, including systolic standard deviation (SD) and average real variability (ARV), were notably higher in the ED group (16.3±3.9vs. 14.6±4.3, p<0.01 and 13.39±7.24vs. 11.5±2.1, p<0.01, respectively). Furthermore, parameters reflecting arterial stiffness including pulse pressure index (PPI) and ambulatory arterial stiffness index (AASI) were higher in the ED group (0.81±0.33vs. 0.73±0.18, p = 0.03 and 0.71±0.09vs. 0.59±0.17, p = 0.014, respectively). Both AASI and ARV were significantly correlated with the severity of ED. This study suggests a significant association between ED severity and altered blood pressure patterns which in part explains the increased risk of CVD among individuals with ED.

Chronobiological disruptions: unravelling the interplay of shift work, circadian rhythms, and vascular health in the context of stroke risk.

Shift work, particularly night shifts, disrupts circadian rhythms and increases stroke risk. This manuscript explores the mechanisms connecting shift work with stroke, focusing on circadian rhythms, hypertension, and diabetes. The circadian system, controlled by different mechanisms including central and peripheral clock genes, suprachiasmatic nuclei (SCN), and pineal gland (through melatonin production), regulates body functions and responds to environmental signals. Disruptions in this system affect endothelial cells, leading to blood pressure issues. Type 2 diabetes mellitus (T2DM) is significantly associated with night shifts, with circadian disturbances affecting glucose metabolism, insulin sensitivity, and hormone regulation. The manuscript examines the relationship between melatonin, insulin, and glucose balance, highlighting pathways that link T2DM to stroke risk. Additionally, dyslipidemia, particularly reduced HDL-c levels, results from shift work and contributes to stroke development. High lipid levels cause oxidative stress, inflammation, and endothelial dysfunction, increasing cerebrovascular risks. The manuscript details the effects of dyslipidemia on brain functions, including disruptions in blood flow, blood-brain barrier integrity, and neural cell death. This comprehensive analysis emphasizes the complex interplay of circadian disruption, hypertension, diabetes, and dyslipidemia in increasing stroke risk among shift workers. Understanding these mechanisms is essential for developing targeted interventions to reduce stroke susceptibility and improve cerebrovascular health in this vulnerable population.

Pineal gland volume in children with intellectual disability.

Pineal gland volume (PGV), which is associated with sleep and circadian rhythm, is known to be changed in some psychiatric disorders such as major depression, mood disorders and schizophrenia. This study aimed to compare the PGV of children with mild and moderate intellectual disability (ID) and healthy children. This multicentre retrospective study included 40 children with ID (patient group), aged 6-12 years and 40 age- and sex-matched healthy children (control group). The children were examined for their sociodemographic characteristics and for PGV using magnetic resonance imaging. The PGV of the patient group was significantly larger than that of the controls (p = 0.023). There was no statistically significant difference in PGV between mild and moderate ID. A moderate and positive correlation was found between Weschler Intelligence Scale for Children-revised (WISC-R) performance score and PGV (p = 0.049, r = 0.313) only in the patient group. In the receiver operating characteristic analysis, the area under the curve was 0.648, and the sensitivity was 70.0%, and the specificity was 60.0%. In conclusion, this study demonstrated that the increased PGV levels were associated with autism spectrum disorder (ASD) and PGV could be a risk factor in the aetiology of ID. Further research with larger sample sizes is needed to clarify this issue.

Chronotherapy in cardiovascular medicine: Optimizing treatment timing based on circadian rhythms

Chronotherapy in cardiovascular medicine: Optimizing treatment timing based on circadian rhythms

Editorial: Roles of the Circadian Rhythms in Metabolic Disease and Health

Editorial: Roles of the Circadian Rhythms in Metabolic Disease and Health

Beyond Lux: methods for species and photoreceptor-specific quantification of ambient light for mammals.

Light is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. Light is commonly measured in lux. However, this employs a spectral weighting function for human luminance and is not suitable for 'non-visual' effects of light or use across species. In humans, a photoreceptor-specific (α-opic) metrology system has been proposed as a more appropriate way of measuring light. Here we establish technology to allow this α-opic measurement approach to be readily extended across mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. We develop a high-throughput method to derive spectral sensitivities for recombinantly expressed mammalian opsins and use it to establish the spectral sensitivity of melanopsin from 13 non-human mammals. We further address the need for simple measurement strategies for species-specific α-opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware multichannel light sensor for 'point and click' measurement. We finally demonstrate that species-specific α-opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species. Our study presents methods for measuring light in species-specific α-opic units that are superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.

Aged hippocampal single-cell atlas screening unveils disrupted neuroglial system in postoperative cognitive impairment.

Glia-neuron interaction is a crucial feature in aged hippocampus during the occurrence of postoperative cognitive impairment. However, the regulatory effects of microglia, astrocytes, and oligodendrocytes in this glia-neuron interaction, the potential mechanisms and gene targets are still to be elucidated. Here, single-cell RNA sequencing was performed to detect the perioperative genomic expression characteristics of neuroglial system in the hippocampus of aged mice, and to investigate the potential cross-cellular mechanisms and valuable treatment options for glia-neuron interaction-related cognitive impairment. We found that postoperative neurons and glia cells exhibited protein dysmetabolism and mitochondrial electron misrouting. Impaired autophagy and circadian rhythm worsened microglia activation/neuroinflammation, and exacerbated these metabolic alterations. Reactive microglia also aggravated astrocyte and oligodendrocyte cytotoxicity through the PGD2/DP and complement pathways, altering glutamate level and synaptic function via the "tripartite synapses" model, and affecting neuronal myelination. Ligand-receptor communication also indicated these synaptic and axonal dysfunctions via enhanced MDK and PTN pathways. Additionally, we found that anesthetic dexmedetomidine hold therapeutic potential within the disrupted neuroglial system. It enhanced neuronal metabolic rebalance (Atf3-related) and reduced neuroinflammation from a multicellular perspective, therefore improving postoperative cognitive impairment. Together, our study proposes an aged hippocampal cell atlas and provides insights into the role of disrupted glia-neuron cycle in postoperative cognitive impairment. Our findings also elucidate the therapeutic potential and mechanism of dexmedetomidine intervention.

Disruption of circadian rhythm as a potential pathogenesis of nocturia.

Increasing evidence suggested the multifactorial nature of nocturia, but the true pathogenesis of this condition still remains to be elucidated. Contemporary clinical medications are mostly symptom based, aimed at either reducing nocturnal urine volume or targeting autonomic receptors within the bladder to facilitate urine storage. The day-night switch of the micturition pattern is controlled by circadian clocks located both in the central nervous system and in the peripheral organs. Arousal threshold and secretion of melatonin and vasopressin increase at night-time to achieve high-quality sleep and minimize nocturnal urine production. In response to the increased vasopressin, the kidney reduces the glomerular filtration rate and facilitates the reabsorption of water. Synchronously, in the bladder, circadian oscillation of crucial molecules occurs to reduce afferent sensory input and maintain sufficient bladder capacity during the night sleep period. Thus, nocturia might occur as a result of desynchronization in one or more of these circadian regulatory mechanisms. Disrupted rhythmicity of the central nervous system, kidney and bladder (known as the brain-kidney-bladder circadian axis) contributes to the pathogenesis of nocturia. Novel insights into the chronobiological nature of nocturia will be crucial to promote a revolutionary shift towards effective therapeutics targeting the realignment of the circadian rhythm.