Significant Circadian Rhythm Research Articles

Circadian Alterations in Brain Metabolism Linked to Cognitive Deficits During Hepatic Ischemia-Reperfusion Injury Using [1H-13C]-NMR Metabolomics

Background: Hepatic ischemia-reperfusion injury (HIRI) is known to affect cognitive functions, with particular concern for its impact on brain metabolic dynamics. Circadian rhythms, as a crucial mechanism for internal time regulation within organisms, significantly influence metabolic processes in the brain. This study aims to explore how HIRI affects hippocampal metabolism and its circadian rhythm differences in mice, and to analyze how these changes are associated with cognitive impairments. Methods: A C57BL/6 male mouse model was used, simulating HIRI through hepatic ischemia-reperfusion surgery, with a sham operation conducted for the control group. Cognitive functions were evaluated using open field tests, Y-maze tests, and novel object recognition tests. Magnetic resonance spectroscopic imaging (MRSI) technology, combined with intravenous injection of [2-13C]-acetate and [1-13C]-glucose, was utilized to analyze metabolic changes in the hippocampus of HIRI mice at different circadian time points (Zeitgeber Time ZT0, 8:00 and ZT12, 20:00). Circadian rhythms regulate behavioral, physiological, and metabolic rhythms through transcriptional feedback loops, with ZT0 at dawn (lights on) and ZT12 at dusk (lights off). Results: HIRI mice exhibited significant cognitive impairments in behavioral tests, particularly in spatial memory and learning abilities. MRSI analysis revealed significant circadian rhythm differences in the concentration of metabolites in the hippocampus, with the enrichment concentrations of lactate, alanine, glutamate, and taurine showing different trends at ZT0 compared to ZT12, highlighting the important influence of circadian rhythms on metabolic dysregulation induced by HIRI. Conclusions: This study highlights the significant impact of HIRI on brain metabolic dynamics in mice, especially in the hippocampal area, and for the first time reveals the differences in these effects within circadian rhythms. These findings not only emphasize the association between HIRI-induced cognitive impairments and changes in brain metabolism but also point out the crucial role of circadian rhythms in this process, offering new metabolic targets and timing considerations for therapeutic strategies against HIRI-related cognitive disorders.

Circadian Rhythm-Dependent Therapy by Composite Targeted Polyphenol Nanoparticles for Myocardial Ischemia-Reperfusion Injury.

Myocardial ischemia-reperfusion (IR) injury is a severe rhythmic disease with a high prevalence in the early morning. IR injury has a significant circadian rhythm in reactive oxygen species (ROS) and inflammation levels. The development of rhythmic drugs has become a priority in myocardial IR injury. In this study, resveratrol (RES) and proanthocyanidins (OPC) were utilized to design nanoparticles (NPs), with hyaluronic acid (HA) as the core, grafted with MMP-targeting peptides to improve delivery to injured myocardial regions (HA-RES-OPC-MMP NPs). NPs significantly scavenged ROS, attenuated inflammation, and activated the rhythm gene. Notably, the difference in therapeutic effects on myocardial IR injury in mice at Zeitgeber time (ZT)1 and ZT13 confirms that NPs are rhythm-dependent drugs. At ZT13, echocardiographic and MRI confirm that IR injury in mice was not as severe as at ZT1, yet NPs were also less effective in treatment. Further, Per1/2 knockout mice confirmed the rhythm-dependent treatment of myocardial IR injury by NPs. Molecular studies have shown that rhythmic characteristics of inflammation and Sirt1 transcript levels are the main reasons for the different rhythmic therapeutic effects of NPs. Circadian rhythm-dependent treatment of HA-RES-OPC-MMP NPs has excellent potential for more precise treatment of myocardial IR injury in the future.

Using proximity loggers in studies of sheep behavior: an estimation of the daily frequency of water consumption

BackgroundProximity loggers are a biotelemetry technology used to quantify animal–animal interactions non-invasively. They are small devices can be affixed to a target animal and detects and records if another device is within a certain distance, which can provide unprecedented insights into individual behavior and interactions with other animals or other aspects of the environment. Proximity loggers also can record the duration and distance between the two or more individuals detected, and have been used to study a diverse array of interactions. Studying drinking behavior in sheep is important for several critical reasons, such as improving animal welfare, enhancing productivity, managing resources efficiently, and ensuring sustainable agricultural practices. The objective of this study was to test the capacity for Bluetooth Low Energy proximity loggers to quantify drinking habits in sheep (n = 7 adult females). At all times, they had access to water from two drinking troughs. Animals wore neck collars that contained a mobile logger, and two stationary loggers were placed under the drinking troughs. To store the records downloaded from the stationary loggers, a gateway was placed close to the troughs. The mobile loggers were programmed as beacons to transmit their ID to the stationary loggers, which were programmed as receivers to scan the proximity of the mobile loggers, record the time, the IDs of the mobile loggers, and the received signal strength of the contact with the mobile loggers.ResultsEwes visited the drinking troughs 2.4 ± 0.5 times per day (rank 1.4–2.9), most frequently (42%) between 0800 and 1000 h, and 84% occurred in the daytime. Mean length of each water intake was 1.72 ± 0.30 min. The cosinor analysis of the distribution of drinking events revealed a significant (P < 0.0001) 24-h circadian rhythm in drinking events, and the acrophase (time of the highest proportion of events) occurred at 1054 h.ConclusionsConsidering that studying water intake in sheep is crucial for optimizing their health, welfare, and management, the proximity loggers were demonstrated to be appropriate for documenting the drinking habits of sheep, and probably, would be suitable for studies of other behaviors that involve approaching other animals or objects.

Domiciliary monitoring of exhaled nitric oxide in the management of asthma: a pilot study.

Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Circadian protein expression patterns in healthy young adults

ObjectivesTo explore how the blood plasma proteome fluctuates across the 24-hour day and identify a subset of proteins that show endogenous circadian rhythmicity. MethodsPlasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. A total of 6916 proteins were analyzed from each sample using the SomaScan aptamer-based multiplexed platform. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that showed circadian rhythmicity in their abundance. ResultsOne thousand and sixty-three (15%) proteins exhibited significant daily rhythmicity. Of those, 431 (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions: it included both known and novel proteins. When models were fitted with two harmonics, an additional 259 (3.7%) proteins exhibited significant endogenous circadian rhythmicity, indicating that some rhythmic proteins cannot be solely captured by a simple sinusoidal model. Overall, we found that the largest number of proteins had their peak levels in the late afternoon/evening, with another smaller group peaking in the early morning. ConclusionsThis study reveals that hundreds of plasma proteins exhibit endogenous circadian rhythmicity in humans. Future analyses will likely reveal novel physiological pathways regulated by circadian clocks and pave the way for improved diagnosis and treatment for patients with circadian disorders and other pathologies. It will also advance efforts to include knowledge about time-of-day, thereby incorporating circadian medicine into personalized medicine.

Circadian Rhythm Alteration of the Core Clock Genes and the Lipid Metabolism Genes Induced by High-Fat Diet (HFD) in the Liver Tissue of the Chinese Soft-Shelled Turtle (Trionyx sinensis).

Physiology disorders of the liver, as it is an important tissue in lipid metabolism, can cause fatty liver disease. The mechanism might be regulated by 17 circadian clock genes and 18 fat metabolism genes, together with a high-fat diet (HFD). Due to their rich nutritional and medicinal value, Chinese soft-shelled turtles (Trionyx sinensis) are very popular among the Chinese people. In the study, we aimed to investigate the influence of an HFD on the daily expression of both the core clock genes and the lipid metabolism genes in the liver tissue of the turtles. The two diets were formulated with 7.98% lipid (the CON group) and 13.86% lipid (the HFD group) to feed 180 juvenile turtles, which were randomly divided into two groups with three replicates per group and 30 turtles in each replicate for six weeks, and the diet experiment was administrated with a photophase regimen of a 24 h light/dark (12L:12D) cycle. At the end of the experiment, the liver tissue samples were collected from nine turtles per group every 3 h (zeitgeber time: ZT 0, 3, 6, 9, 12, 15, 18, 21 and 24) for 24 h to investigate the daily expression and correlation analysis of these genes. The results showed that 11 core clock genes [i.e., circadian locomotor output cycles kaput (Clock), brain and muscle arnt-like protein 1 and 2 (Bmal1/2), timeless (Tim), cryptochrome 1 (Cry2), period2 (Per2), nuclear factor IL-3 gene (Nfil3), nuclear receptor subfamily 1, treatment D, member 1 and 2 (Nr1d1/2) and retinoic acid related orphan receptor α/β/γ β and γ (Rorβ/γ)] exhibited circadian oscillation, but 6 genes did not, including neuronal PAS domain protein 2 (Npas2), Per1, Cry1, basic helix-loop-helix family, member E40 (Bhlhe40), Rorα and D-binding protein (Dbp), and 16 lipid metabolism genes including fatty acid synthase (Fas), diacylglycerol acyltransferase 1 (Dgat1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), Low-density lipoprotein receptor-related protein 1-like (Ldlr1), Lipin 1 (Lipin1), Carnitine palmitoyltransferase 1A (Cpt1a), Peroxisome proliferator activation receptor α, β and γ (Pparα/β/γ), Sirtuin 1 (Sirt1), Apoa (Apoa1), Apolipoprotein B (Apob), Pyruvate Dehydrogenase kinase 4 (Pdk4), Acyl-CoA synthase long-chain1 (Acsl1), Liver X receptors α (Lxrα) and Retinoid X receptor, α (Rxra) also demonstrated circadian oscillations, but 2 genes did not, Scd and Acaca, in the liver tissues of the CON group. However, in the HFD group, the circadian rhythms' expressional patterns were disrupted for the eight core clock genes, Clock, Cry2, Per2, Nfil3, Nr1d1/2 and Rorβ/γ, and the peak expression of Bmal1/2 and Tim showed delayed or advanced phases. Furthermore, four genes (Cry1, Per1, Dbp and Rorα) displayed no diurnal rhythm in the CON group; instead, significant circadian rhythms appeared in the HFD group. Meanwhile, the HFD disrupted the circadian rhythm expressions of seven fat metabolism genes (Fas, Cpt1a, Sirt1, Apoa1, Apob, Pdk4 and Acsl1). Meanwhile, the other nine genes in the HFD group also showed advanced or delayed expression peaks compared to the CON group. Most importantly of all, there were remarkably positive or negative correlations between the core clock genes and the lipid metabolism genes, and their correlation relationships were altered by the HFD. To sum up, circadian rhythm alterations of the core clock genes and the lipid metabolism genes were induced by the high-fat diet (HFD) in the liver tissues of T. sinensis. This result provides experimental and theoretical data for the mass breeding and production of T. sinensis in our country.

The role of the SIRT1-BMAL1 pathway in regulating oxidative stress in the early development of ischaemic stroke

Oxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00–05:59); subgroup 2 (06:00–11:59); subgroup 3 (12:00–17: 59); and subgroup 4 (18:00–23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P < 0.05). Among the four subgroups, the content of MDA, IL-6, and TNF-α was highest in patients with ischaemic stroke onset from subgroup 2 (06:00–11:59), while the expression levels of SOD, BMAL1, and SIRT1 were lowest in patients with ischaemic stroke in subgroup 2. Additionally, myeloperoxidase (MPO) reached the highest value showing the same trends consistent with MDA, IL-6, and TNF-ɑ and opposite trends consistent with SOD, BMAL1, and SIRT1. However, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), immediate blood glucose, immediate diastolic blood pressure, immediate systolic blood pressure, and homocysteine (HCY) did not show any statistically significant circadian rhythm changes (P > 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO.

Effects of Light and Feeding on Expressions of Clock Genes and Metabolic Genes in the Ridgetail Shrimp, Exopalaemon carinicauda

The changes of the circadian clock genes expression, growth, and muscle composition in Exopalaemon carinicauda under different photoperiods and feeding time were investigated by real-time fluorescence quantitative PCR and muscle biochemical composition analysis, respectively. Results showed that four clock genes of Clock, Cry1, Tim, and Per2 showed significant circadian rhythms in both eyestalk and hepatopancreas. Their expression rhythms were highly correlated with the photoperiod in the eyestalk, but in the hepatopancreas, it was significantly correlated with the feeding time. Moreover, the expressions of several metabolic genes were also variable; adipose triglyceride lipase (ATGL) and amyloglucosidase (AGL) changed significantly with the shift of feeding time, whereas methionine synthase (MS) and succinate dehydrogenase (SDH) changed significantly with the photoperiod. This reflected the close relationship between the metabolic and circadian clock in E. carinicauda; Alterations in photoperiod or feeding time lead to changes in the biological clock systems, which affects the daily expression of metabolic genes at the downstream metabolic pathway and closely correlates their expression rhythms with epi-environmental factors such as feeding. It can be seen from the results that the feeding was also a significant factor that affected the crude protein and crude fat contents in muscle tissue of E. carinicauda; their highest values (18.69% ± 0.13%, 1.81% ± 0.02%) were also occurred in the treatment with feeding at 19:00. Differences in muscle composition through a similar mechanism of action, i.e., the biological clock system are affected by the feeding and then regulated changes in downstream metabolic processes. As a result, the optimized conditions for the cultivation of E. carinicauda were a short light-phase photoperiod (8L : 16D) with feeding after sunset (19:00).

Sleep-independent circadian rhythm of aldosterone secretion in healthy young adults

ObjectiveA diurnal variation in urine output has been described in humans, whereby it is lowest at night. Fluid balance hormones such as vasopressin and aldosterone as well as urine output have a diurnal variation. Although the diurnal variation of vasopressin results in part from a circadian rhythm, the variation in aldosterone has until recently been reported to be due to the sleep/wake cycle. The present study used a specialized protocol to explore whether aldosterone has an underlying circadian rhythm. MethodsTen healthy participants (average age 23.1) were enrolled in the 57.3-hour protocol that included an 8-hour baseline sleep episode, 40 hours in constant routine conditions (wakefulness, food and fluid intake, posture, and dim light), and a 9.3-hour recovery sleep. Blood samples for aldosterone were taken every 4 hours. Cosinor analysis was performed on the constant routine data to test the effect of the sleep/wake cycle on overall aldosterone secretion. ResultsThere was a significant circadian rhythm during the 40-hour constant routine, independent of sleep, with aldosterone higher at the end of the biological night and lower at the end of the biological day. When analyzing data from the entire 57.3-hour protocol and controlling for this circadian rhythm, aldosterone concentration was significantly higher during the recovery night following the 40-hour sleep deprivation compared to the night spent awake. ConclusionWe found a significant endogenous circadian rhythm in the secretion of aldosterone, independent of sleep. In addition, as shown previously, there was a significant effect of the sleep/wake cycle on aldosterone secretion.

Effects of eyestalk ablation on growth, feeding behavior, movement and circadian gene expression in Haliotis discus hannai

The present study aimed to investigate the effects of eyestalk ablation on growth, feeding behavior, circadian movement activity, and circadian gene expression in the abalone Haliotis discus hannai. Abalones were divided into two groups: eyestalk-ablated (EA) and control (C), and were cultured for 60 days. Results showed that the EA group exhibited significantly higher growth rates in body weight compared to the C group. However, the EA group also had a higher mortality rate, indicating the negative consequences of eyestalk ablation. The feeding rate was significantly higher in the EA group, especially during nocturnal feeding, suggesting that eyestalk ablation may specifically affect nocturnal feeding behavior in abalone. Both EA and C groups displayed rhythmic oscillations in movement activity, with no significant differences in mesor and amplitude. Nevertheless, the peak of populational movement proportion in the EA group occurred approximately 2 h earlier than that in the C group. Transcriptome analysis identified 417 circadian genes, with the most significant enrichment found in the growth-related thyroid hormone signaling pathway. The expression of five core clock genes (clock, cry, rho, tipin, per) exhibited significant circadian rhythms in H. discus hannai, while their rhythmic oscillation significance was weaker in the EA group, except for the tipin transcript. These findings reveal that eyestalk ablation affects growth, feeding and locomotor behavior, and clock gene expression in abalone, providing valuable insights for understanding the circadian regulatory mechanisms and physiological ecological adaptations of abalone. However, due to its harmful effects on animal welfare and the limited promotion of growth, this technology is not advocated for use in aquaculture practices.

Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.

Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR). 18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation. A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19). A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.

Circadian Variation in Human Milk Hormones and Macronutrients.

There is an inadequate understanding of the daily variations in hormones and macronutrients in human milk (HM), and sample collection protocols vary considerably from study to study. To investigate changes in these milk components across 24 h, 22 lactating women collected small milk samples before and after each breastfeed or expression from each breast. Test weighing was used to determine the volume of HM consumed in each feed. The concentrations of leptin, adiponectin, insulin, fat, and glucose were measured, and the intakes were calculated. A linear mixed model was fitted to assess within-feed and circadian variation in HM feed volume and concentration, and intakes of several components. The average infant intake of HM was 879 g/24 h. Significantly higher pre-feed concentrations were found for adiponectin and glucose and lower post-feed concentrations were found for insulin and fat. Significant circadian rhythms were displayed for leptin, adiponectin, insulin, glucose (both concentration and intake), fat concentration, and milk volume. These findings demonstrate the necessity for setting up standardised and rigorous sampling procedures that consider both within-feed and circadian variations in HM components to gain a more precise understanding of the impacts of these components on infant health, growth and development.

Artificial induction of circadian rhythm by combining exogenous BMAL1 expression and polycomb repressive complex 2 inhibition in human induced pluripotent stem cells.

Understanding the physiology of human-induced pluripotent stem cells (iPSCs) is necessary for directed differentiation, mimicking embryonic development, and regenerative medicine applications. Pluripotent stem cells (PSCs) exhibit unique abilities such as self-renewal and pluripotency, but they lack some functions that are associated with normal somatic cells. One such function is the circadian oscillation of clock genes; however, whether or not PSCs demonstrate this capability remains unclear. In this study, the reason why circadian rhythm does not oscillate in human iPSCs was examined. This phenomenon may be due to the transcriptional repression of clock genes resulting from the hypermethylation of histone H3 at lysine 27 (H3K27), or it may be due to the low levels of brain and muscle ARNT-like 1 (BMAL1) protein. Therefore, BMAL1-overexpressing cells were generated and pre-treated with GSK126, an inhibitor of enhancer of zest homologue 2 (EZH2), which is a methyltransferase of H3K27 and a component of polycomb repressive complex 2. Consequently, a significant circadian rhythm following endogenous BMAL1, period 2 (PER2), and other clock gene expression was induced by these two factors, suggesting a candidate mechanism for the lack of rhythmicity of clock gene expression in iPSCs.

0017 Obstructive sleep apnea is associated with altered circadian rhythms in systolic blood pressure at rest and during exercise

Abstract Introduction Obstructive sleep apnea (OSA) is associated with an increased risk for major adverse cardiovascular events (MACE), such as sudden cardiac death. MACE is more frequent in the morning in the general population but more frequent in the middle of the night in people with OSA. Whether these differences are associated with changes in circadian rhythms of blood pressure regulation is unknown. We tested if circadian rhythms in systolic blood pressure (SBP) during rested wakefulness and in response to a standardized mild exercise are disturbed in people with OSA compared to healthy controls (HC). Methods We studied 39 participants (HC [n=25, age 52.8±7.8 {mean±SD} years], (OSA [n=14, 50.6±6.6 years]) during ten identical recurring 5-h 20-min behavioral cycles in dim light and in an environment free of time cues. SBP was measured in the supine position during rested wakefulness followed by while seated at rest and during mild-intensity (heart rate at 50% heart rate reserve using the Karvonen formula) exercise on a static cycle ergometer. Circadian phases were determined relative to the dim-light melatonin onset. We performed mixed-model cosinor analyses to test whether the groups differed in their SBP rhythms during rested wakefulness and in their BP responses to exercise. Results Melatonin levels or phases relative to clock time were not different between groups (p=0.17), suggesting similar timing of central circadian clock outputs. There was an overall rhythm (p&amp;lt; 0.001) and a trend to group x circadian phase interaction for resting SBP (p=0.10). A separate group analysis showed a significant circadian rhythm in SBP in HC (p&amp;lt; 0.001) with a peak in the evening but no evident circadian rhythm in people with OSA (p=0.17). There was no circadian phase x exercise reactivity interaction between groups, but overall, exercise reactivity of SBP was significantly higher in people with OSA (+4mmHg, p=0.001). Conclusion OSA is characterized by a blunted circadian rhythm in resting blood pressure and an exaggerated blood pressure reactivity to exercise. Mechanisms for these rhythm changes should be investigated further. Support (if any) Support: NIH F32HL163232, R01HL125893, R01HL163232, R35HL155681, R01HL156948, ULTR00128, Oregon Institute of Occupational Health Sciences.

Circadian rhythm disturbances in mood disorders: characterisation and clinical impact

IntroductionCircadian rhythms, defined as endogenous oscillations that regulate metabolism, physiology and behaviour, may be frequently disrupted in mood disorders, influencing their clinical presentation and course (Srinivasan V. et al. World J Biol Psychiatry. 2006;7(3):138-151).ObjectivesTo characterise circadian rhythm disruptions in a population of patients with mood disorders, analysing clinical and course differences in subjects with and without clinically significant circadian rhythm alterationsMethodsPatients selected for this cross-sectional study were assessed with CGI-BP, HAM-D, MRS, and PANSS. Circadian rhythm disturbances were evaluated with BRIAN. Patients with clinically relevant circadian rhythm disturbances were defined as BRIAN &gt; 36 (Mondin TC et al. J Psychiatr Res. 2017;84:98-104). Bivariate analyses were subsequently performed to compare subgroups of patients.ResultsIn our study, 61 subjects with DD or DB were enrolled. The overall mean BRIAN test score was 40.08 ± 10.26. When comparing the BRIAN test scores, both total and subscales, between subjects with DB and DD, social rhythms were significantly more altered in subjects with DB (8.63 ± 2.90 VS 6.80 ± 2.11, p=0.034). Subjects with disruption of circadian rhythms displayed greater severity of depressive symptoms (mean total HAM-D test score 16.06±8.61 VS 8.94±5.85; p&lt;0.003, mean CGI-BP severity of depression test score 3.14±1.68 VS 1.88±1.11; p&lt;0.010) and with a longer duration of untreated illness (6.14±8.64 VS 2.53±6.28; p= 0.040).ConclusionsAlterations in circadian rhythms should be routinely investigated in all individuals with mood disorders, especially BD, and may represent a transdiagnostic psychopathological construct that defines a more severe disease phenotype.Disclosure of InterestNone Declared

Effects of constant light and dark conditions on the locomotor activity, body mass, and body temperature rhythms of Eurasian Tree Sparrows (Passer montanus)

Light is an essential environmental cue influencing the endogenous circadian clocks that regulate behavioral and physiological processes in animals. Despite extensive research on the circadian rhythms of avian behavior and physiology, the mechanisms by which they adapt and adjust to abnormal photoperiod conditions, such as artificial light, have yet to be fully elucidated. Here, the circadian rhythms of the body mass, activity, and core and peripheral body temperatures of the Eurasian Tree Sparrow (Passer montanus, ETS)—a diurnal passerine—were examined under three different lighting conditions: constant light (LL), constant darkness (DD), and normal light–dark cycles (LD). Our results showed that the activity, body mass, core, tarsometatarsus, and eye temperatures of the ETSs varied significantly with treatment, time, and the interaction between treatment and time; however, there was no significant change in body mass in response to the interaction between time and treatment. Under LD conditions, the ETSs exhibited significant circadian rhythms in activity and core, tarsometatarsus, and eye temperatures. Under LL conditions, only the core temperature exhibited significant rhythmicity. Under DD conditions, there were no significant circadian rhythms in activity, body mass, and eye temperature; however, the core and tarsometatarsus temperatures remained rhythmic. Our results indicate that the core body temperature rhythm of ETS is endogenous and can be maintained under abnormal photoperiods. In contrast, the activity and body surface temperature, uncoupled from the core body temperature under abnormal photoperiod conditions, strongly depend on light. These results differ from those of other diurnal avian species, suggesting a unique coping mechanism of ETS in response to an abnormal photoperiod.

A Circadian Rhythm of Visual Sensitivity in the American Lobster, Homarus americanus.

AbstractTo determine whether eyes of American lobsters (Homarus americanus) are more sensitive to light at night than during the day, electroretinograms were continuously recorded from 23 adult lobsters for at least 3 days (range: 3 to 9 days) in constant darkness. A green light-emitting diode, mounted 10 cm away from the eyes, was briefly flashed every 2 minutes to evoke the electroretinogram. The average increase in the response to a light flash, between the minimum during the subjective day and the maximum during the subjective night, was 105.6% ± 38.8%; and there was a statistically significant difference between day and night responses. This change in visual sensitivity took place while lobsters were held in constant darkness, suggesting that it was due to the influence of a circadian clock. The average period (tau) for the 10 animals that expressed significant circadian rhythms was 23.4 ± 0.8 hours. Previous studies have demonstrated that lobsters have circadian clocks that influence their locomotor activity; and the present data suggest that this is also true for their eyes, leading to an increase in their visual sensitivity at night, when they are typically most active.

The circadian system modulates the cortisol awakening response in humans.

In humans, circulating cortisol usually peaks 30-60 min after awakening from nocturnal sleep, this is commonly referred to as the cortisol awakening response (CAR). We examined the extent to which the CAR is influenced by the circadian system, independent of behaviors including sleep. We examined the CAR in 34 adults (20 female) using two complementary multiday in-laboratory circadian protocols performed in dim light, throughout which behavioral factors were uniformly distributed across the 24-hour circadian cycle. Protocol 1 consisted of 10 identical consecutive 5-hour 20-minute sleep/wake cycles, and protocol 2 consisted of 5 identical consecutive 18-hour sleep/wake cycles. Salivary melatonin was used as the circadian phase marker (0° = dim light melatonin onset). During each sleep/wake cycle, salivary cortisol was measured upon scheduled awakening and 50-minutes later, with the change in cortisol defined as the CAR. Cosinor analyses were used to detect any significant circadian rhythmicity in the CAR. In secondary analyses, we adjusted the models for time awake before lights on, total sleep time, percent of rapid eye movement (REM) sleep, and percent of non-rapid eye movement (NREM) sleep. Both protocols revealed a similar circadian rhythm in the CAR, with peaks occurring at a circadian phase corresponding to 3:40-3:45 a.m., with no detectable CAR during the circadian phases corresponding to the afternoon. In addition to the sinusoidal component of the circadian rhythm, total sleep time was also associated with the CAR for protocol 1. The percent of sleep spent in REM or NREM sleep were not associated with the CAR in either protocol. Our results show that the CAR exhibits a robust circadian rhythm that persists even after adjusting for prior sleep. Presuming that the CAR optimizes physiological responses to the anticipated stressors related to awakening, these findings may have implications for shift workers who wake up at unusual circadian phases. A blunted CAR in shift workers upon awakening in the evening may result in diminished responses to stressors.

Genome-wide identification and expression analysis of fatty acid-binding proteins (FABPs) in Chinese perch Siniperca chuatsi and their circadian rhythm responses to cadmium exposure

Fatty acid-binding proteins (FABPs) function as fatty acid chaperones, and they play a key role in lipid metabolism. The diversity of fabp gene family members is important for different fatty acid absorption and transport. In the present study, we identified 13 fabp genes from Chinese perch (Siniperca chuatsi). The spatiotemporal expression profiles of these 13 Sc-fabp genes, their circadian rhythm expression characteristics in intestine, and transcriptional regulation under cadmium exposure were investigated. Phylogenetic analysis indicated that the teleost-specific genome duplication event made a contribution to the expansion of Sc-fabp genes. The protein coding regions of all the 13 Sc-fabp genes were composed of 4 exons. These 13 genes exhibited similar protein length, but a low identity in protein sequences. The tissue expression profiles of most fabp genes in Chinese perch (Sc-fabp2a, Sc-fabp2b, Sc-fabp3, Sc-fabp6a, Sc-fabp7a, and Sc-fabp7b) were consistent with those of their orthologous genes in mammalian, but the Sc-fabp1, Sc-fabp6ba, and Sc-fabp6bb showed distinct tissue expression patterns from their orthologous genes in mammalian. The total expression level of Sc-fabps was increased with embryonic development, but it was decreased significantly after hatching. Sc-fabp1, Sc-fabp3, Sc-fabp11a, and Sc-fabp11b were the mainly expressed subtypes in embryonic development stages. Under natural conditions, the expression of these 4 subtypes Sc-fabp1, Sc-fabp2a, Sc-fabp2b, and Sc-fabp6a exhibited significant circadian rhythm in intestine, and their peak expression levels were observed from ZT 8.83 h to ZT 13.54 h. Cadmium exposure resulted in the up-regulation of fabp gene expression and the loss of circadian rhythm in Chinese perch intestine. Our results provide reference for further investigation of the biological functions of fabp gene subtypes in fish.

Circadian rhythm of markers of bone turnover in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have a high risk of bone fractures. A circadian rhythmicity in turnover and mineralization of bone appears to be of importance for bone health. In CKD disturbances in the circadian rhythm of various functions has been demonstrated and indeed the circadian rhythm in the mineral metabolism is disturbed. The aim of the present study was to compare the circadian rhythm of bone turnover markers in ten patients with CKD to ten healthy controls. Bone turnover markers (C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase 5b, N-terminal propeptide of type I procollagen, bone alkaline phosphatase and osteocalcin) were measured every third hour for 24 h. All bone turnover markers displayed a significant circadian rhythm in both groups and there were no significant differences in the rhythmicity between the two groups (no group*time interaction). As expected, due to the reduced renal clearance, the overall level of C-terminal telopeptide of type I collagen and osteocalcin was higher in CKD compared to the healthy controls. The present study suggests that disturbances in the circadian rhythm of bone turnover do not explain the metabolic bone disease and increased risk of fractures in CKD.