Clock Gene Expression Research Articles

Pheromone-mediated command from the female to male clock induces and synchronizes circadian rhythms of the moth Spodoptera littoralis

To extract any adaptive benefit, the circadian clock needs to be synchronized to the 24-h day-night cycles. We have investigated if it is a general property of the brain's circadian clock to recognize social interactions as external time givers. Sociosexual interactions with the opposite sex are universal, prevalent even in the lives of solitary animals. The solitary adult life of the Spodoptera littoralis moth is singularly dedicated to sex, offering an ideal context for exploring the impact of sociosexual cues on circadian timekeeping. We have identified specific olfactory cues responsible for social entrainment, revealing a surprisingly strong influence of pheromone-mediated remote sociosexual interactions on circadian rhythms. Males' free-running rhythms are induced and synchronized by the sex pheromone that the female releases in a rhythmic fashion, highlighting a hierarchical relation between the female and male circadian oscillators. Even a single pulse of the sex pheromone altered clock gene expression in the male brain, surpassing the effect of light on the clock. Our finding of a daytime-dependent, lasting impact of pheromone on male's courtship efficacy indicates that circadian timing in moths is a trait under sexual selection. We have identified specific components of the sex-pheromone blend that lack mate-attractive property but have powerful circadian effects, providing rationale for their continued retention by the female. We show that such volatiles, when shared across sympatric moth species, can trigger communal synchronization. Our results suggest that the sex pheromone released by female moths entrains males' behavioral activity rhythm to ensure synchronized timing of mating.

Metabolic plasticity and obesity-associated changes in diurnal postexercise metabolism in mice

BackgroundCircadian disruption is widespread and increases the risk of obesity. Timing of therapeutic interventions may promote coherent and efficient gating of metabolic processes and restore energy homeostasis. AimTo characterize the diurnal postexercise metabolic state in mice and to identify the influence of diet-induced obesity on identified outcomes. MethodsC57BL6/NTac male mice (6 wks of age) were fed a standard chow or high-fat diet for 5 weeks. At week 5, mice were subjected to a 60-min (16 m/min, 5 % incline) running bout (or sham) during the early rest (day) or early active (night) phase. Tissue and serum samples were collected immediately post-exercise (n = 6/group). In vivo glucose oxidation was measured after oral administration of 13C-glucose via 13CO2 exhalation analysis in metabolic cages. Basal and isoproterenol-stimulated adipose tissue lipolysis was assessed ex vivo for 1 h following exercise. ResultsLean mice displayed exercise-timing-specific plasticity in metabolic outcomes, including phase-specificity in systemic glucose metabolism and adipose-tissue-autonomous lipolytic activity depending on time of day. Conversely, obesity impaired temporal postexercise differences in whole-body glucose oxidation, as well as the phase- and exercise-mediated induction of lipolysis in isolated adipose tissue. This obesity-induced alteration in diurnal metabolism, as well as the indistinct response to exercise, was observed concomitant with disruption of core clock gene expression in peripheral tissues. ConclusionsOverall, high-fat fed obese mice exhibit metabolic inflexibility, which is also evident in the diurnal exercise response. Our study provides physiological insight into exercise timing-dependent aspects in the dynamic regulation of metabolism and the influence of obesity on this biology.

Social jet lag impairs exercise volume and attenuates physiological and metabolic adaptations to voluntary exercise training.

Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice (n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance (P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice (P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice (P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance.NEW & NOTEWORTHY In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations.

Cellular and molecular organization of the Drosophila foregut

The animal foregut is the first tissue to encounter ingested food, bacteria, and viruses. We characterized the adult Drosophila foregut using transcriptomics to better understand how it triages consumed items for digestion or immune response and manages resources. Cell types were assigned and validated using GFP-tagged and Gal4 reporter lines. Foregut-associated neuroendocrine cells play a major integrative role by coordinating gut activity with nutrition, the microbiome, and circadian cycles; some express clock genes. Multiple epithelial cell types comprise the proventriculus, the central foregut organ that secretes the peritrophic matrix (PM) lining the gut. Analyzing cell types synthesizing individual PM layers revealed abundant mucin production close to enterocytes, similar to the mammalian intestinal mucosa. The esophagus and salivary gland express secreted proteins likely to line the esophageal surface, some of which may generate a foregut commensal niche housing specific gut microbiome species. Overall, our results imply that the foregut coordinates dietary sensing, hormonal regulation, and immunity in a manner that has been conserved during animal evolution.

(057) Influence of Circadian Disruption on Erectile Function in Chronic Jet-Lagged Young Rats

Abstract Introduction Sleep is crucial during the developing stage of one’s life and has been associated with physical activity. However, as the number of 24-hour stores such as convenience stores and supermarkets have increased, along with increased internet usage, people have developed the habit of staying up late, resulting in sleep deprivation due to disruption in the light-dark cycle. Jet lag is widely used in animal models for inducing irregular circadian rhythms. Chronic jet lagged model animals are known to develop a variety of disorders. Objective To investigate the influences of chronic jet lag on erectile function in rats in order to elucidate the effects of irregular circadian rhythms on future sexual function. Methods 4-week-old rats underwent randomly assigned to remain either under the control light/dark cycle (Cont group) or under chronic light/dark shift schedule to simulate the conditions of chronic jet lag (CJL group). The shift-lag protocol consisted of 8 h light/dark phase advances repeated every 3 days for 4 weeks. Erectile function was examined at 1, 2, and 4 weeks post CJL treatment. After 4 weeks of CJL treatment, the rats were returned to control light/dark cycle for 4 and 8 weeks, as CJL(4w)+Rest(4w) group and CJL(4w)+Rest(8w) group, and erectile function was examined correspondingly. Erectile function was tested using intracavernous pharmacotherapy (ICP) measurements, and endothelial function was tested through an isometric tension study. Western blot analysis was used to assess the levels of endothelial nitric oxide (eNOS) and phosphorylated eNOS (p-eNOS). Additionally, mRNA expressions of clock genes (Bmal1 and Cry 1) and growth factors (TGF-β1 and ICAM-1) were tested using real-time PCR. Results The ICP/MAP ratio was significantly lower in the CJL group (0.35 ± 0.05) at 4 weeks than in the control group (0.66 ± 0.05) (P &amp;lt; 0.05). CJL group exhibited significantly lower testosterone levels, Bmal1, Cry 1, TGF-β1, and ICAM-1 expression, and p-eNOS and cGMP levels. The ICP/MAP ratio in the CJL(4w)+Rest(4w) group (0.47 ± 0.06) was lower than that in the control group (P &amp;lt; 0.01) whereas the ratio in the CJL(4w)+Rest(8w) group (0.81 ± 0.03) was similar to that in the control group (P &amp;gt; 0.05). Conclusions In this study, chronic jet lagged (4 weeks) rats exhibited a decreased ICP/MAP ratio, reduced testosterone level, and decreased p-eNOS expression, indicating the development of erectile dysfunction (ED). Upon 8 weeks of normal light/dark shift schedule, erectile function was recovered. This study suggests that irregular circadian rhythms induced by repeated jet lag, especially in childhood, may affect the production of sex hormones and erectile function in the future. Therefore, it is necessary for children to follow a regular circadian rhythm and healthy lifestyle. Disclosure No.

Diel Cycle Proteomics: Illuminating Molecular Dynamics in Purple Bacteria for Optimized Biotechnological Applications.

Circadian rhythms, characterized by approximately 24 h cycles, play a pivotal role in enabling various organisms to synchronize their biological activities with daily variations. While ubiquitous in Eukaryotes, circadian clocks remain exclusively characterized in Cyanobacteria among Prokaryotes. These rhythms are regulated by a core oscillator, which is controlled by a cluster of three genes: kaiA, kaiB, and kaiC. Interestingly, recent studies revealed rhythmic activities, potentially tied to a circadian clock, in other Prokaryotes, including purple bacteria such as Rhodospirillum rubrum, known for its applications in fuel and plastic bioproduction. However, the pivotal question of how light and dark cycles influence protein dynamics and the expression of putative circadian clock genes remains unexplored in purple non-sulfur bacteria. Unraveling the regulation of these molecular clocks holds the key to unlocking optimal conditions for harnessing the biotechnological potential of R. rubrum. Understanding how its proteome responds to different light regimes-whether under continuous light or alternating light and dark cycles-could pave the way for precisely fine-tuning bioproduction processes. Here, we report for the first time the expressed proteome of R. rubrum grown under continuous light versus light and dark cycle conditions using a shotgun proteomic analysis. In addition, we measured the impact of light regimes on the expression of four putative circadian clock genes (kaiB1, kaiB2, kaiC1, kaiC2) at the transcriptional and translational levels using RT-qPCR and targeted proteomic (MRM-MS), respectively. The data revealed significant effects of light conditions on the overall differential regulation of the proteome, particularly during the early growth stages. Notably, several proteins were found to be differentially regulated during the light or dark period, thus impacting crucial biological processes such as energy conversion pathways and the general stress response. Furthermore, our study unveiled distinct regulation of the four kai genes at both the mRNA and protein levels in response to varying light conditions. Deciphering the impact of the diel cycle on purple bacteria not only enhances our understanding of their ecology but also holds promise for optimizing their applications in biotechnology, providing valuable insights into the origin and evolution of prokaryotic clock mechanisms.

Light quality-dependent roles of REVEILLE proteins in the circadian system.

Several closely related Myb-like activator proteins are known to have partially redundant functions within the plant circadian clock, but their specific roles are not well understood. To clarify the function of the REVEILLE 4, REVEILLE 6, and REVEILLE 8 transcriptional activators, we characterized the growth and clock phenotypes of CRISPR-Cas9-generated single, double, and triple rve mutants. We found that these genes act synergistically to regulate flowering time, redundantly to regulate leaf growth, and antagonistically to regulate hypocotyl elongation. We previously reported that increasing intensities of monochromatic blue and red light have opposite effects on the period of triple rve468 mutants. Here, we further examined light quality-specific phenotypes of rve mutants and report that rve468 mutants lack the blue light-specific increase in expression of some circadian clock genes observed in wild type. To investigate the basis of these blue light-specific circadian phenotypes, we examined RVE protein abundances and degradation rates in blue and red light and found no significant differences between these conditions. We next examined genetic interactions between RVE genes and ZEITLUPE and ELONGATED HYPOCOTYL5, two factors with blue light-specific functions in the clock. We found that the RVEs interact additively with both ZEITLUPE and ELONGATED HYPOCOTYL5 to regulate circadian period, which suggests that neither of these factors are required for the blue light-specific differences that we observed. Overall, our results suggest that the RVEs have separable functions in plant growth and circadian regulation and that they are involved in blue light-specific circadian signaling via a novel mechanism.

Chronic intermittent hypoxia leads to disruption of clock genes expression in mouse lung tissues: Potential consequences on lung cell senescence

Chronic intermittent hypoxia leads to disruption of clock genes expression in mouse lung tissues: Potential consequences on lung cell senescence

Treadmill training impacts the skeletal muscle molecular clock after ischemia stroke in rats

ObjectiveStroke is frequently associated with muscle mass loss. Treadmill training is considered the most effective treatment for sarcopenia. Circadian rhythms are closely related to exercise and have been extensively studied. The skeletal muscle has its molecular clock genes. Exercise may regulate skeletal muscle clock genes. This study evaluated the effects of early treadmill training on the skeletal muscle molecular clock machinery in rats with stroke and determined the relationship of these changes with exercise-induced improvements in skeletal muscle health. Materials and methodsOverall, 168 Sprague-Dawley rats were included in this study. We established an ischemic stroke rat model of sarcopenia. Finally, 144 rats were randomly allocated to four groups (36 per group): normal, sham, middle cerebral artery occlusion, and training. Neurological scores, rotating rod test, body weight, muscle circumference, wet weight, and hematoxylin-eosin staining were assessed. Twenty-four rats were used for transcriptome sequencing. Gene and protein expressions of skeletal muscles, such as brain muscle arnt-like 1, period 1, and period 2, were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays. ResultsNeurological function scores and rotating rod test results improved after treadmill training. Nine differentially expressed genes were identified by comparing the sham group with the hemiplegic side of the model group. Seventeen differentially expressed genes were identified between the hemiplegic and non-hemiplegic sides. BMAL1, PER1, and PER2 mRNA levels increased on both sides after treadmill training. BMAL1 expression increased, and PER1 expression decreased on both sides, whereas PER2 expression decreased on the hemiplegic side but increased on the non-hemiplegic side. ConclusionTreadmill training can mitigate muscle loss and regulate skeletal muscle clock gene expression following ischemic stroke. Exercise affects the hemiplegic side and has a positive regulatory effect on the non-hemiplegic side.

Circadian patterns and photoperiodic modulation of clock gene expression and neuroendocrine hormone secretion in the marine teleost Larimichthys crocea

ABSTRACT The light/dark cycle, known as the photoperiod, plays a crucial role in influencing various physiological activities in fish, such as growth, feeding and reproduction. However, the underlying mechanisms of this influence are not fully understood. This study focuses on exploring the impact of different light regimes (LD: 12 h of light and 12 h of darkness; LL: 24 h of light and 0 h of darkness; DD: 0 h of light and 24 h of darkness) on the expression of clock genes (LcClocka, LcClockb, LcBmal, LcPer1, LcPer2) and the secretion of hormones (melatonin, GnRH, NPY) in the large yellow croaker, Larimichthys crocea. Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assays were utilized to assess how photoperiod variations affect clock gene expression and hormone secretion. The results indicate that changes in photoperiod can disrupt the rhythmic patterns of clock genes, leading to phase shifts and decreased expression. Particularly under LL conditions, the pineal LcClocka, LcBmal and LcPer1 genes lose their rhythmicity, while LcClockb and LcPer2 genes exhibit phase shifts, highlighting the importance of dark phase entrainment for maintaining rhythmicity. Additionally, altered photoperiod affects the neuroendocrine system of L. crocea. In comparison to the LD condition, LL and DD treatments showed a phase delay of GnRH secretion and an acceleration of NPY synthesis. These findings provide valuable insights into the regulatory patterns of circadian rhythms in fish and may contribute to optimizing the light environment in the L. crocea farming industry.

Effects of circadian clock disruption on gene expression and biological processes in Aedes aegypti

BackgroundThis study explores the impact of disrupting the circadian clock through a Cycle gene knockout (KO) on the transcriptome of Aedes aegypti mosquitoes. The investigation aims to uncover the resulting alterations in gene expression patterns and physiological processes.ResultsTranscriptome analysis was conducted on Cyc knockout (AeCyc-/-) and wild-type mosquitoes at four time points in a light-dark cycle. The study identified system-driven genes that exhibit rhythmic expression independently of the core clock machinery. Cyc disruption led to altered expression of essential clock genes, affecting metabolic processes, signaling pathways, stimulus responses and immune responses. Notably, gene ontology enrichment of odorant binding proteins, indicating the clock's role in sensory perception. The absence of Cyc also impacted various regulation of metabolic and cell cycle processes was observed in all time points.ConclusionsThe intricate circadian regulation in Ae. aegypti encompasses both core clock-driven and system-driven genes. The KO of Cyc gene instigated extensive gene expression changes, impacting various processes, thereby potentially affecting cellular and metabolic functions, immune responses, and sensory perception. The circadian clock's multifaceted involvement in diverse biological processes, along with its role in the mosquito's daily rhythms, forms a nexus that influences the vector's capacity to transmit diseases. These insights shed light on the circadian clock's role in shaping mosquito biology and behavior, opening new avenues for innovative disease control strategies.

Persistence of clock gene expression in peripheral blood in dogs maintained under different photoperiod schedules

ABSTRACT Dogs are the common pets adopted by humans, and their circadian behavior and physiology are influenced by human habits. In many families, there is a change of lifestyle with respect to the natural daylight (NDL) cycle. Exposure to constant light disrupts some central and peripheral circadian rhythms. The aim of the present study was to improve the knowledge about the circadian changes of clock components in the peripheral blood in dogs housed under NDL and constant light (LL) conditions. Blood samples were collected on five female Beagle dogs (2 years old, 14 ± 0.5 kg) every 4 hours for a 24-hour period during an NDL (Sunrise 05:05 h – Sunset 20:55 h) and 24-hour period of constant light (LL). Blood samples were stored in a PAX gene Blood RNA Tube, real-time RT-quantitative polymerase chain reaction was performed to determine Clock, Per1–3, and Cry1–2 gene expression. During the NDL, all genes investigated showed robust diurnal daily rhythmicity. During the constant light, only Clock maintained its daily rhythmicity. Clock acrophase was observed close to sunrise (ZT 0) and was statistically different from the other clock genes except for Per3. Per3 daily oscillations were not statistically significant. No differences were observed among the clock genes tested in the amplitude and robustness values. Our results can be considered preliminary data to provide new insights into the adaptation mechanism of the canine peripheral circadian clock. The persistence of Clock gene expression during the LL indicated the presence of an endogenously generated signal in blood. Because peripheral blood is an easily accessible sample in dogs, the analysis of clock gene expression in this tissue could be useful to investigate the adaptive capacity of this species housed in different environmental conditions linked to the owner’s lifestyle.

The interplay between the circadian clock and abiotic stress responses mediated by ABF3 and CCA1/LHY

Climate change is a global concern for all life on our planet, including humans and plants. Plants' growth and development are significantly affected by abiotic stresses, including adverse temperature, inadequate or excess water availability, nutrient deficiency, and salinity. The circadian clock is a master regulator of numerous developmental and metabolic processes in plants. In an effort to identify new clock-related genes and outputs through bioinformatic analysis, we have revealed that CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) play a crucial role in regulating a wide range of abiotic stress responses and target ABSCISIC ACID RESPONSIVE ELEMENTS-BINDING FACTOR3 (ABF3), a key transcription factor in the plant hormone Abscisic acid (ABA)-signaling pathway. Specifically, we found that CCA1 and LHY regulate the expression of ABF3 under diel conditions, as well as seed germination under salinity. Conversely, ABF3 controls the expression of core clock genes and orchestrates the circadian period in a stress-responsive manner. ABF3 delivers the stress signal to the central oscillator by binding to the promoter of CCA1 and LHY. Overall, our study uncovers the reciprocal regulation between ABF3 and CCA1/LHY and molecular mechanisms underlying the interaction between the circadian clock and abiotic stress. This finding may aid in developing molecular and genetic solutions for plants to survive and thrive in the face of climate change.

Principles of synaptic encoding of brainstem circadian rhythms.

Circadian regulation of autonomic tone and reflex pathways pairs physiological processes with the daily light cycle. However, the underlying mechanisms mediating these changes on autonomic neurocircuitry are only beginning to be understood. The brainstem nucleus of the solitary tract (NTS) and adjacent nuclei, including the area postrema and dorsal motor nucleus of the vagus, are key candidates for rhythmic control of some aspects of the autonomic nervous system. Recent findings have contributed to a working model of circadian regulation in the brainstem which manifests from the transcriptional, to synaptic, to circuit levels of organization. Vagal afferent neurons and the NTS possess rhythmic clock gene expression, rhythmic action potential firing, and our recent findings demonstrate rhythmic spontaneous glutamate release. In addition, postsynaptic conductances also vary across the day producing subtle changes in membrane depolarization which govern synaptic efficacy. Together these coordinated pre- and postsynaptic changes provide nuanced control of synaptic transmission across the day to tune the sensitivity of primary afferent input and likely govern reflex output. Further, given the important role for the brainstem in integrating cues such as feeding, cardiovascular function and temperature, it may also be an underappreciated locus in mediating the effects of such non-photic entraining cues. This short review focuses on the neurophysiological principles that govern NTS synaptic transmission and how circadian rhythms impacted them across the day.

Prostaglandin F2α Affects the Cycle of Clock Gene Expression and Mouse Behavior.

Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor (Ptgfr) has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of Ptgfr-KO (B6.129-Ptgfrtm1Sna) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in Ptgfr-KO mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (Cry1), which is related to the circadian cycle. Moreover, the expression of Cry1, Cry2, and Period2 (Per2) mRNA were significantly altered in the mouse liver in Ptgfr-KO mice under DD. In the wild-type mouse, the plasma prostaglandin F2α (PGF2α) levels showed a circadian rhythm under a 12 h cycle of light-dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of Per2::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF2α is important for driving clock genes, thus suggesting the involvement of PGF2α- and Ptgfr-targeting drugs in the biological clock cycle.

Cellular iron depletion enhances behavioral rhythm by limiting brain Per1 expression in mice.

Disturbances in the circadian rhythm are positively correlated with the processes of aging and related neurodegenerative diseases, which are also associated with brain iron accumulation. However, the role of brain iron in regulating the biological rhythm is poorly understood. In this study, we investigated the impact of brain iron levels on the spontaneous locomotor activity of mice with altered brain iron levels and further explored the potential mechanisms governing these effects invitro. Our results revealed that conditional knockout of ferroportin 1 (Fpn1) in cerebral microvascular endothelial cells led to brain iron deficiency, subsequently resulting in enhanced locomotor activity and increased expression of clock genes, including the circadian locomotor output cycles kaput protein (Clock) and brain and muscle ARNT-like 1 (Bmal1). Concomitantly, the levels of period circadian regulator 1 (PER1), which functions as a transcriptional repressor in regulating biological rhythm, were decreased. Conversely, the elevated brain iron levels in APP/PS1 mice inhibited autonomous rhythmic activity. Additionally, our findings demonstrate a significant decrease in serum melatonin levels in Fpn1cdh5 -CKO mice compared with the Fpn1flox/flox group. In contrast, APP/PS1 mice with brain iron deposition exhibited higher serum melatonin levels than the WT group. Furthermore, in the human glioma cell line, U251, we observed reduced PER1 expression upon iron limitation by deferoxamine (DFO; iron chelator) or endogenous overexpression of FPN1. When U251 cells were made iron-replete by supplementation with ferric ammonium citrate (FAC) or increased iron import through transferrin receptor 1 (TfR1) overexpression, PER1 protein levels were increased. Additionally, we obtained similar results to U251 cells in mouse cerebellar astrocytes (MA-c), where we collected cells at different time points to investigate the rhythmic expression of core clock genes and the impact of DFO or FAC treatment on PER1 protein levels. These findings collectively suggest that altered iron levels influence the circadian rhythm by regulating PER1 expression and thereby modulating the molecular circadian clock. In conclusion, our study identifies the regulation of brain iron levels as a potential new target for treating age-related disruptions in the circadian rhythm.

Assessment of circadian rhythm markers and clock genes expression in patients with Chronic Insomnia

Assessment of circadian rhythm markers and clock genes expression in patients with Chronic Insomnia

Light pollution disrupts circadian clock gene expression in two mosquito vectors during their overwintering dormancy

Artificial light at night (ALAN) is an increasingly important form of environmental disturbance as it alters Light:Dark cycles that regulate daily and seasonal changes in physiology and phenology. The Northern house mosquito (Culex pipiens) and the tiger mosquito (Aedes albopictus) enter an overwintering dormancy known as diapause that is cued by short days. These two species differ in diapause strategy: Cx. pipiens diapause as adult females while Ae. albopictus enter a maternally-programmed, egg diapause. Previous studies found that ALAN inhibits diapause in both species, but the mechanism is unknown. As the circadian clock is implicated in the regulation of diapause in many insects, we examined whether exposure to ALAN altered the daily expression of core circadian cloc genes (cycle, Clock, period, timeless, cryptochrome 1, cryptochrome 2, and Par domain protein 1) in these two species when reared under short-day, diapause-inducing conditions. We found that exposure to ALAN altered the abundance of several clock genes in adult females of both species, but that clock gene rhythmicity was maintained for most genes. ALAN also had little effect on clock gene abundance in mature oocytes that were dissected from female Ae. albopictus that were reared under short day conditions. Our findings indicate that ALAN may inhibit diapause initiation through the circadian clock in two medically-important mosquitoes.

A pilot study on the expression of circadian clock genes in the alveolar bone of mice with periodontitis

ABSTRACT This study aimed to investigate the expression of circadian clock genes in mouse alveolar bone, and the possible reasons for these changes. Fifty C57 mice were orally inoculated with P. gingivalis, establishing a model of periodontitis using healthy mice as controls. The alveolar bone of both groups was taken for micro-computed tomography scanning to measure the amount of attachment loss, and the relative expression of mRNA in each clock gene and periodontitis related inflammatory factor was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). After the establishment of the mouse model, the height of alveolar bone in the periodontitis group was significantly lower than that in the normal group (p < 0.05). The relative transcriptional level of Bmal1, Per2, and Cry1 mRNA was in the circadian rhythm in the normal group (p ≤ 0.05), while in the periodontitis group, its circadian rhythm disappeared and the transcriptional level characteristics were changed. Interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN-γ) mRNA transcriptional level were elevated in the periodontitis group compared to the normal group. In conclusion, the mRNA transcriptional level of Bmal1, Per2, and Cry1 in alveolar bone of normal mice has circadian rhythm, but the rhythm disappears under the condition of periodontitis, and the cause of its occurrence may be related to inflammatory cytokines.

Mucosal Genes Encoding Clock, Inflammation and Their Mutual Regulators Are Disrupted in Pediatric Patients with Active Ulcerative Colitis.

Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to characterize the expression of clock and inflammation genes, and their mutual regulatory genes in treatment-naïve pediatric patients with UC. Using the Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) platform and R algorithms, we analyzed rectal biopsy transcriptomic data from two cohorts (206 patients with UC vs. 20 healthy controls from the GSE-109142 study, and 43 patients with UC vs. 55 healthy controls from the GSE-117993 study). We compared gene expression levels and correlation of clock genes (BMAL1, CLOCK, PER1, PER2, CRY1, CRY2), inflammatory genes (IκB, IL10, NFκB1, NFκB2, IL6, TNFα) and their mutual regulatory genes (RORα, RORγ, REV-ERBα, PGC1α, PPARα, PPARγ, AMPK, SIRT1) in patients with active UC and healthy controls. The clock genes BMAL1, CLOCK, PER1 and CRY1 and the inflammatory genes IκB, IL10, NFκB1, NFκB2, IL6 and TNFα were significantly upregulated in patients with active UC. The genes encoding the mutual regulators RORα, RORγ, PGC1α, PPARα and PPARγ were significantly downregulated in patients with UC. A uniform pattern of gene expression was found in healthy controls compared to the highly variable expression pattern in patients with UC. Among the healthy controls, inflammatory genes were positively correlated with clock genes and they all showed reduced expression. The difference in gene expression levels was associated with disease severity and endoscopic score but not with histological score. In patients with active UC, clock gene disruption is associated with abnormal mucosal immune response. Disrupted expression of genes encoding clock, inflammation and their mutual regulators together may play a role in active UC.