Circadian Rhythm Pattern Research Articles

Predictors of the development of abnormal patterns of circadian blood pressure rhythm in patients with hypertension after a new coronavirus infection

Objective. To determine the predictors of the development of abnormal patterns of circadian blood pressure (BP) rhythm in patients with arterial hypertension (AH) after a new coronavirus infection (NСVI). Materials and methods. The study is a comparative clinical research of the same patients with hypertension before and after NCVI with retrospective evaluation of the data. Within 2 years from 842 patients with cardiovascular risk factors, according to the inclusion and non-inclusion criteria 70 patients with target levels of office BP, home monitoring and 24-hour blood pressure monitoring (ABPM) on the background of a continuous antihypertensive therapy were included in the study. Abnormal patterns of circadian BP were recorded after NCVI during ABPM in all of them. All patients with hypertension underwent a complete examination before and after NCVI. Results. After NCVI in patients with AH who had achieved the target ranges of office BP before its development, at home measurement and ABPM against the background of continuous antihypertensive therapy with high adherence to treatment, in more than 50 % of patients BP readings were not in the target values, in more than 50 % of the examined patients, BP variability was higher than the permissible values, in 73 % of patients the average daily BP was above 53 mm Hg. Abnormal patterns of circadian BP rhythm in patients with hypertension after NCVI were detected in 61.5 %: "Non-dipper" in 28.6 %; "Night-dipper" – in 21.9 %, masked nocturnal hypertension – in 17.1 %. Conclusion. The indicative significance of the development of abnormal patterns of circadian BP rhythm in patients with hypertension after NCVI was demonstrated by 3 qualitative indicators: glomerular filtration rate with cystatin C 60 ml/min/1.73 m2, cardio-ankle vascular index (CAVI) ≥ 9, and a high frequency of AGT gene polymorphism – T/T genotype (in 54.3 % of patients).

Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.

The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability. A mouse model with inducible deletion of the p53-encoding gene, Trp53, in skeletal muscle was generated using the Cre-loxP-system. A detailed analysis of nutrient metabolism in mice with control and knockout genotypes was performed under ad libitum fed and fasting conditions and in exercised mice. Acute deletion of p53 in myofibres of mice activated catabolic nutrient usage pathways even under ad libitum fed conditions, resulting in significantly increased overall energy expenditure (+10.6%; P=0.0385) and a severe nutrient deficit in muscle characterized by depleted intramuscular glucose and glycogen levels (-62,0%; P<0.0001 and -52.7%; P<0.0001, respectively). This was accompanied by changes in marker gene expression patterns of circadian rhythmicity and hyperactivity (+57.4%; P=0.0068). These metabolic changes occurred acutely, within 2-3days after deletion of Trp53 was initiated, suggesting a rapid adaptive response to loss of p53, which resulted in a transient increase in lactate release to the circulation (+46.6%; P=0.0115) from non-exercised muscle as a result of elevated carbohydrate mobilization. Conversely, an impairment of proteostasis and amino acid metabolism was observed in knockout mice during fasting. During endurance exercise testing, mice with acute, muscle-specific Trp53 inactivation displayed an early exhaustion phenotype with a premature shift in fuel usage and reductions in multiple performance parameters, including a significantly reduced running time and distance (-13.8%; P=0.049 and -22.2%; P=0.0384, respectively). These findings suggest that efficient nutrient conservation is a key element of normal metabolic homeostasis that is sustained by p53. The homeostatic state in metabolic tissues is actively maintained to coordinate efficient energy conservation and metabolic flexibility towards nutrient stress. The acute deletion of Trp53 unlocks mechanisms that suppress the activity of nutrient catabolic pathways, causing substantial loss of intramuscular energy stores, which contributes to a fasting-like state in muscle tissue. Altogether, these findings uncover a novel function of p53 in the short-term regulation of nutrient metabolism in skeletal muscle and show that p53 serves to maintain metabolic homeostasis and efficient energy conservation.

Prolonged Blue Light Exposure Does Not Elicit Adverse Changes to Physical Activity in Male Mice

Color plays a role in human and animal circadian rhythm patterns, behaviors, and emotional responses. Environments containing blue colors improve information storage in humans and reproductive success in animals; however, environments containing blue light influence behavioral and emotional responses in rodents and humans in adverse ways. Exposure to blue light alters sleeping patterns, induces the stress response, and elicits depressive behaviors. These initial responses then affect awake time functionality and productivity. Under normal physiological conditions, mice, when provided access to an in-cage running wheel, exhibit high levels of nocturnal physical activity behavior. It is unknown if this nocturnal behavior changes after prolonged blue light exposure. Therefore, this project's hypothesis is wheel running utilization decreases after exposure to blue light during the diurnal restful period in the normally nocturnal mouse. The purpose of this study was to expose mice to overhead blue LED lights during the daytime rest period and to examine nighttime physical activity patterns. Daily wheel running distance, duration, and speed monitoring in C57BL/6j male mice (n=12) occurred for 21 days. During the second week of the study, an experimental group (n=6) underwent blue light-emitting diode (LED) light exposure, and a control group (n=6) experienced white LED light exposure at the same intensity. The lights were on a 12-hour light/dark cycle at full brightness during the exposure period. Differences in wheel running distance, duration, and speed following exposure to blue LED light were assessed via individual two-way (group by phase of study) ANOVAs. Blue LED light exposure did not appear to affect average daily wheel running distance [F=0.42, p=0.57], duration [F=0.79, p=0.42], or speed [F=0.08, p=0.87]. Following exposure to blue LED light during the restful diurnal period, wheel running remained stable. This lack of effect indicates that mechanisms may exist to protect mice from the adverse effects associated with blue light exposure, especially as it pertains to participating in routine physical activity. These postulated mechanisms may allow robust participation in physical activity-related behaviors in these animals and represent a potential biological regulator that could aid in mitigating the adverse effects of blue light exposure experienced in humans. All funding for this research was provided by the Union University Department of Biology. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

0001 Circadian Rest-Activity Rhythm Patterns and Physical Performance in Community-Dwelling Older Men

0001 Circadian Rest-Activity Rhythm Patterns and Physical Performance in Community-Dwelling Older Men

Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement

ObjectivesSalivary cortisol reflects the biologically active form of serum cortisol, offering a noninvasive evaluation method for the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) is known for its specificity, immunoassays (IA) are commonly used because of their simplicity. This study aimed to assess the performance of salivary cortisol measurement using both IA and LC-MS/MS in comparison to serum-free cortisol measurement. MethodsAssay results for 188 saliva and 94 serum samples from 47 participants were analyzed. Salivary samples collected at different time points were analyzed using IA and LC-MS/MS. Serum samples were analyzed for cortisol, cortisol-binding globulin, and free cortisol. The statistical analyses included correlations and method comparisons. ResultsThe diurnal salivary cortisol profiles exhibited a comparable circadian rhythm pattern; however, the concentrations measured using IA were consistently higher than those measured using LC-MS/MS. The correlation analysis revealed robust associations among salivary cortisol (IA), salivary cortisol (LC-MS/MS), and serum-free cortisol levels (LC-MS/MS). However, the method comparison revealed a systematic bias between IA and LC-MS/MS in salivary cortisol measurement. ConclusionsThis study contributes to the ongoing debate on assay techniques by affirming the suitability of IA and LC-MS/MS for salivary cortisol measurement to assess dynamic changes in HPA axis activity. The identified systematic bias emphasizes the importance of selecting methods based on specific research or clinical requirements.

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.

Differential Regulation of Circadian Clock Genes by UV-B Radiation and 1,25-Dihydroxyvitamin D: A Pilot Study during Different Stages of Skin Photocarcinogenesis.

Increasing evidence points at an important physiological role of the timekeeping system, known as the circadian clock (CC), regulating not only our sleep-awake rhythm but additionally many other cellular processes in peripheral tissues. It was shown in various cell types that environmental stressors, including ultraviolet B radiation (UV-B), modulate the expression of genes that regulate the CC (CCGs) and that these CCGs modulate susceptibility for UV-B-induced cellular damage. It was the aim of this pilot study to gain further insights into the CCs' putative role for UV-B-induced photocarcinogenesis of skin cancer. Applying RT-PCR, we analyzed the expression of two core CCGs (brain and muscle ARNT-like 1 (Bmal1) and Period-2 (Per2)) over several time points (0-60 h) in HaCaT cells with and without 1,25-dihydroxyvitamin D (D3) and/or UV-B and conducted a cosinor analysis to evaluate the effects of those conditions on the circadian rhythm and an extended mixed-effects linear modeling to account for both fixed effects of experimental conditions and random inter-individual variability. Next, we investigated the expression of these two genes in keratinocytes representing different stages of skin photocarcinogenesis, comparing normal (Normal Human Epidermal Keratinocytes-NHEK; p53 wild type), precancerous (HaCaT keratinocytes; mutated p53 status), and malignant (Squamous Cell Carcinoma SCL-1; p53 null status) keratinocytes after 12 h under the same conditions. We demonstrated that in HaCaT cells, Bmal1 showed a robust circadian rhythm, while the evidence for Per2 was limited. Overall expression of both genes, but especially for Bmal1, was increased following UV-B treatment, while Per2 showed a suppressed overall expression following D3. Both UVB and 1,25(OH)2D3 suggested a significant phase shift for Bmal1 (p < 0.05 for the acrophase), while no specific effect on the amplitude could be evidenced. Differential effects on the expression of BMAL1 and Per2 were found when we compared different treatment modalities (UV-B and/or D3) or cell types (NHEK, HaCaT, and SCL-1 cells). Comparing epidermal keratinocytes representing different stages of skin photocarcinogenesis, we provide further evidence for an independently operating timekeeping system in human skin, which is regulated by UV-B and disturbed during skin photocarcinogenesis. Our finding that this pattern of circadian rhythm was differentially altered by treatment with UV-B, as compared with treatment with D3, does not support the hypothesis that the expression of these CCGs may be regulated via UV-B-induced synthesis of vitamin D but might be introducing a novel photoprotective property of vitamin D through the circadian clock.

Examining Human-Smartphone Interaction as a Proxy for Circadian Rhythm in Patients With Insomnia: Cross-Sectional Study.

The sleep and circadian rhythm patterns associated with smartphone use, which are influenced by mental activities, might be closely linked to sleep quality and depressive symptoms, similar to the conventional actigraphy-based assessments of physical activity. The primary objective of this study was to develop app-defined circadian rhythm and sleep indicators and compare them with actigraphy-derived measures. Additionally, we aimed to explore the clinical correlations of these indicators in individuals with insomnia and healthy controls. The mobile app "Rhythm" was developed to record smartphone use time stamps and calculate circadian rhythms in 33 patients with insomnia and 33 age- and gender-matched healthy controls, totaling 2097 person-days. Simultaneously, we used standard actigraphy to quantify participants' sleep-wake cycles. Sleep indicators included sleep onset, wake time (WT), wake after sleep onset (WASO), and the number of awakenings (NAWK). Circadian rhythm metrics quantified the relative amplitude, interdaily stability, and intradaily variability based on either smartphone use or physical activity data. Comparisons between app-defined and actigraphy-defined sleep onsets, WTs, total sleep times, and NAWK did not reveal any significant differences (all P>.05). Both app-defined and actigraphy-defined sleep indicators successfully captured clinical features of insomnia, indicating prolonged WASO, increased NAWK, and delayed sleep onset and WT in patients with insomnia compared with healthy controls. The Pittsburgh Sleep Quality Index scores were positively correlated with WASO and NAWK, regardless of whether they were measured by the app or actigraphy. Depressive symptom scores were positively correlated with app-defined intradaily variability (β=9.786, SD 3.756; P=.01) and negatively correlated with actigraphy-based relative amplitude (β=-21.693, SD 8.214; P=.01), indicating disrupted circadian rhythmicity in individuals with depression. However, depressive symptom scores were negatively correlated with actigraphy-based intradaily variability (β=-7.877, SD 3.110; P=.01) and not significantly correlated with app-defined relative amplitude (β=-3.859, SD 12.352; P=.76). This study highlights the potential of smartphone-derived sleep and circadian rhythms as digital biomarkers, complementing standard actigraphy indicators. Although significant correlations with clinical manifestations of insomnia were observed, limitations in the evidence and the need for further research on predictive utility should be considered. Nonetheless, smartphone data hold promise for enhancing sleep monitoring and mental health assessments in digital health research.

Cloning, tissue distribution, and effects of different circadian rhythms on the mRNA expression levels of circadian clock genes Per1a and Per1b in Phoxinus lagowskii

This study describes the cloning and characterization of Period 1a and Period 1b genes and the analysis of their mRNA and protein expression in Amur minnow (Phoxinus lagowskii) after exposure to different light cycles. The full-length P. lagowskii Per1a and Per1b genes encode proteins consisting of 1393 and 1409 amino acids, and share high homology with the per1 genes of other freshwater fish species. The Per1a and Per1b genes were widely expressed within the brain, eye, and peripheral tissues. The acrophase of the Per1a gene in the pituitary gland occurred during the dark phase at ZT15 (zeitgeber time 15, 12 L: 12 D) and ZT18 (8 L, 16 D), whereas the acrophase of the Per1b gene in the pituitary gland was observed during the light phase. Our study suggests that the expression of Per1a and Per1b in P. lagowskii varied depending on differences in circadian rhythm patterns. The results of our dual-luciferase reporter assays demonstrated that the P. lagowskii Per1b gene enhances the activation of NF-κB. This study is the first to examine the circadian clock gene Per1a and Per1b in the high-latitude fish P. lagowskii, offering valuable insights into the effects of different light periods on this fish species.

Yeast Hydrolysate Inhibits Lipid Accumulation via Regulation of Lipid Accumulation-Related Genes in a Drosophila Model of High-Sugar Diet-Induced Obesity.

The increasing frequency of processed food consumption has led to the higher ingestion of sugar, increasing the risk of chronic diseases, such as obesity. Yeast hydrolysates (YHs) inhibit body fat accumulation. However, the action mechanism of YH in relation to high-sugar diet-induced obesity is still unclear. Therefore, this study aimed to evaluate the biological effects of YH on lipid accumulation and verify behavioral changes and carbohydrate metabolic gene regulation in high-sugar diet-fed fruit flies. Adult male flies (Drosophila melanogaster; 2-5 days old) were exposed to 20% sucrose for obesity induction. In high-sugar-fed Drosophila, the effect of YH was compared with that of yeast extract. The effects of YH on body conditions and lipid droplet size were quantified and analyzed. Behavioral factors were evaluated by analyzing circadian rhythm patterns and neurotransmitter content, and a molecular approach was used to analyze the expression of metabolism-related genes. Dietary supplementation with YH did not reduce total sugar content, but significantly decreased the triglyceride (TG) levels in Drosophila. A behavioral analysis showed that the total number of night-time activities increased significantly with YH treatment in a dose-dependent manner. In addition, YH effectively regulated the gene expression of insulin-like peptides related to carbohydrate metabolism as well as genes related to lipogenesis. The TG content was significantly reduced at a YH concentration of 0.5%, confirming that the active compound in YH effectively suppresses fat accumulation. These findings support that YH is a potential anti-obesity food material via regulating carbohydrate metabolism in Drosophila.

Genome-Wide Identification of 5-HT Receptor Gene Family in Razor Clam Sinonovacula constricta and Their Circadian Rhythm Expression Analysis.

Serotonin (5-HT) is primarily distributed in the gastrointestinal and central nervous systems, where it plays a crucial role in regulating various physiological functions such as digestion, reproduction and establishing animal emotions. 5-HT is an effective oxytocin widely used in molluscan aquaculture, and its physiological functions are performed by binding to corresponding 5-HT receptors (5-HTRs). In this study, seven 5-HTR genes of Sinonovacula constricta (Sc5-HTRs) were identified and analyzed, and they were designated as Sc5-HT1A, Sc5-HT1D, Sc5-HT2-1, Sc5-HT2-2, Sc5-HT2-3, Sc5-HT4 and Sc5-HT6. Phylogenetic analysis showed that the seven Sc5-HTRs were conserved among mollusks, and the Sc5-HTRs were all transmembrane proteins. The seven Sc5-HTR genes were distributed on chromosome 1, 2, 13 and 14. After injecting 5-HT, there was a significant increase in mRNA expression levels of Sc5-HT1A (p < 0.05) and Sc5-HT2-3 (p < 0.01), while Sc5-HT4 decreased significantly (p < 0.01) compared to control groups which might be effective 5-HT receptors. Furthermore, two of the receptors (Sc5-HT2-3 and Sc5-HT4) were expressed in the circadian rhythm patterns, indicating their potential influence on the nocturnal spawning of S. constricta. Overall, these findings provide a theoretical basis for understanding the structures and functions of 5-HTR gene family members, and may facilitate the artificial propagation of mollusks.

Circadian rhythm disorders in patients with advanced cancer: a scoping review.

Circadian rhythms can be demonstrated in several biomarkers and behavioural activities, with rhythmical patterns occurring roughly over a 24-h period. Circadian disorders occur in patients with cancer and may be associated with poor clinical outcomes. This scoping review aimed to identify circadian rhythm research and reporting practices, circadian rhythm patterns, circadian rhythm disorders, and relevant associations of circadian rhythm disorders in patients with advanced cancer. Studies involved adult patients with locally advanced or metastatic cancer and used objective measures of circadian rhythmicity. Two independent authors completed initial screening of title and abstracts, full text reviews, data extraction, and data checking. A total of 98 articles were highlighted in the scoping review, which utilised physical activity measures (actigraphy and polysomnography), biomarkers (cortisol and melatonin), or a combination. Several circadian rhythms are commonly disordered amongst patients with advanced cancer and have significant implications for symptom burden, quality of life, and survival. It remains unclear which patients are most at risk of a circadian rhythm disorder. Significant heterogeneity exists in research and reporting practices. Standardising this approach may address discrepancies in the current literature and allow for research to focus on the most relevant parameters and approaches to improving circadian rhythmicity.

0615 Racial/Ethnic and Sex Differences in Circadian Rest-Activity Rhythm Patterns: Findings from a Sample of the US Population

Abstract Introduction Circadian disruptions are associated with increased risk for morbidity and mortality. However, it is unclear whether these associations vary by race/ethnicity. We aim to explore, 1) Examine whether rest-activity rhythm (RAR) patterns vary across race/ethnicity among a representative sample of the US adult population, and 2) Examine the interaction of race/ethnicity and sex in RAR patterns. Methods The study was based on the National Health and Nutrition Examination Survey (2013–2014) with data from participants who wore a physical activity monitor (PAM ActiGraph accelerometer model GT3X+) continuously for seven consecutive days. After excluding pregnant participants and those with sleep minutes &amp;lt; 120 and &amp;gt;1200, the analytic sample included was 4,722 adults. The cosinor method was used based on PAM minutes time-series data to RAR outcome variables: mesor, amplitude, acrophase. and robustness. The main predictor of interest was race/ethnicity (Asian, Black, Hispanic, multi/other, and White). A sex-race/ethnicity interaction was tested to assess if racial/ethnic differences in RAR patterns differ between males and females. Other covariates included were age, marital status education federal poverty level, and employment status. Eight adjusted Generalized linear models (GLM) : four with race/ethnicity as the main predictors and four multiplicative interaction models with the product term of race/ethnicity and sex. An adjusted Wald test was used to test for interaction. Results Compared with White adults, Hispanic adults had increased mesor levels (ß=0.10; 95% CI:0.07;0.13), increased RAR amplitude (ß=0.10; 95% CI:0.06;0.13), and increased robustness (ß=0.07; 95% CI:0.03;0.11) whereas Black adults had decreased amplitude (ß=-0.11; 95% CI:-0.16;-0.07) and decreased robustness ( (ß= -0.14; 95% CI:-0.20; -0.09) compared to White adults. Similarly, Asians had decreased amplitude (ß=-0.06; 95% CI:-0.10;-0.01) and decreased robustness (ß=-0.11; 95% CI:-0.16; -0.06). A significant sex-race/ethnicity interaction was found for amplitude F(4,12)=3.94;p=0.029 and robustness (4,12)=6.02;p&amp;lt; 0.001. Conclusion RAR is associated with race/ethnicity, and this association varies by sex. Notably, Hispanic adults had increased mesor, amplitude, and robustness compared to Whites. Conversely, Black and Asian populations shared decreased amplitude and robustness compared to Whites. Future studies may consider further investigation of circadian health by race/ethnicity and sex for community intervention. Support (if any) K01HL135452, K07AG052685, R01AG072644, R01HL152453, R01MD007716, R01HL142066, R01AG067523, R01AG056031, and R01AG075007

Integrative analysis of the association between circadian rhythm and lupus nephritis.

Lupus nephritis (LN) is an autoimmune nephropathy associated with systemic lupus erythematosus. Circadian rhythms are involved in the development of several diseases, especially inflammation-related diseases, but their relationship with LN is unclear. This was an integrative bioinformatics study. The expression profile from glomeruli, tubular interstitium and renal whole tissue samples was used to assess the expression levels and relevance of circadian rhythm-related genes. To screen for circadian rhythm-related signatures, we employed the LASSO and SVM-RFE algorithms. A consensus clustering algorithm was used to classify LN patients into two circadian rhythm patterns (cluster A and cluster B). We made immune cell infiltration analysis. We used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific differentially expressed genes. Nephroseq data were used to observe the relationship between genes and renal function. We found more significant differences in circadian rhythm-related gene expression in LN glomeruli compared with tubulointerstitial and whole-kidney tissues. We established a circadian rhythm-related signature consisting of eight genes that can easily distinguish LN from healthy individuals. Patients in cluster A were associated with B-cell-dominated immunity, whereas patients in cluster B were associated with T-cell-dominated immunity. As most of the patients with proliferative LN combined with membranous LN belonged to cluster B, patients in cluster B may have more severe renal pathology compared with patients in cluster A. Fifteen circadian rhythm-related genes associated with LN and LN typing were screened using the WGCNA algorithm, with COL1A2 and DOCK2 associated with renal prognosis. This study found that circadian rhythms are associated with the occurrence of LN, providing new ideas for the development of new LN treatment options from the perspective of circadian rhythms.

The effect of brain-derived neurotrophic factor Val66Met polymorphism on adolescent activity and rest rhythms, circadian preferences and attentional performance

BackgroundVariations in circadian regulating mechanisms generate different individual preferences in respect of sleep and activity timing, which are known as chronotypes. In this sense, specifically during adolescence, there is a greater tendency for an eveningness chronotype. One factor that has been shown to have an impact on circadian rhythm patterns, as well as on some aspects of cognitive function, is the relatively common Val66Met (rs6265) polymorphism in the human brain-derived neurotrophic factor gene. ObjectiveThis study aimed to evaluate the effect of the BDNF Val66Met polymorphism on the performance of adolescents in attentional tests, circadian preferences and activity-rest rhythm. Methods85 healthy high school students completed the Morningness-Eveningness Questionnaire to assess their circadian preferences; were evaluated using the Psychological Battery for Attention Assessment; and were categorized as carriers and non-carriers of the rs6265 polymorphism using the TaqMan rt-PCR technique. A subsample of 42 students had their activity/rest rhythm recorded by actigraphy for nine days from which sleep parameters were estimated. ResultsCircadian preference did not affect attentional performance (p > 0.1), but the time that the students attended school had an impact on all types of attention with morning shift students scoring higher, regardless of chronotype (p < 0.05). The presence of the BDNF Val66Met polymorphism was associated only with alternate attention performance (p < 0.05). Regarding actigraphy evaluation, the carriers of the polymorphism demonstrated significantly higher total time in bed, total sleep time, social jetlag, and earlier sleep onset. ConclusionsThe results indicate some degree of adaptation in the students' attentional performance, according to their school schedules. The presence of BDNF polymorphism demonstrated a counterintuitive impact on attentional performance, comparing to previous findings. The findings reinforce the effect of genetic traits on sleep-wake rhythm parameters, when objectively evaluated.

Circadian Rhythm Types in Individuals with Diabetic Macular Edema

Background and Hypothesis:Diabetic Retinopathy (DR) is the leading cause of vision loss in patients with diabetes. Diabeticmacular edema (DME) can be associated with any stage of DR, causing thickening and swelling of the macula, leading to vision impairment. Circadian rhythm, the body’s natural clock thatgoverns physiological processes and dictates our sleep-wake cycle, is known to be affected by DR and DME. This study hypothesizes that DME will be associated with a more extreme circadian rhythm type.&#x0D; Methods:Individuals 18 years or older with a diagnosis of type I or type II diabetes complicated by DMEwere given a 19-item Morningness-Eveningness Questionnaire (MEQ) to determine their circadian rhythm and sleep patterns. Information regarding demographics, metabolic parameters, diabetes, visual acuity and DME severity was collected.&#x0D; Results:In this ongoing study, we compiled data from 54 individuals out of a targeted enrollment of 160. Overall, the MEQ scores characterized more individuals as morning types, followed by intermediate and evening types. The preliminary analysis shows a weak, insignificant positive correlation with retinal thickness in the right eye and a weak, insignificant negative in the left eye. In addition, a weak, insignificant negative correlation was also observed between MEQ and right eye visual acuity, with the opposite trend occurring in the left eye. DME variables such as mean central foveal thickness decreased insignificantly in right eyes from morning to evening groups but increased in the left eye.&#x0D; Conclusion and Potential Impact: Our study suggests DME individuals are mostly morning type instead of evening type. However, there is no strong relationship between MEQ scores and DME parameters. As we recruit more individuals in the future, we hope to establish a more significant relationship that could improve our understanding of how circadian rhythms and DME are interconnected and could lead to new treatments.

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus.

The mammalian central circadian clock, located in the suprachiasmatic nucleus (SCN), coordinates the timing of physiology and behavior to local time cues. In the SCN, second messengers, such as cAMP and Ca2+, are suggested to be involved in the input and/or output of the molecular circadian clock. However, the functional roles of second messengers and their dynamics in the SCN remain largely unclear. In the present study, we visualized the spatiotemporal patterns of circadian rhythms of second messengers and neurotransmitter release in the SCN. Here, we show that neuronal activity regulates the rhythmic release of vasoactive intestinal peptides from the SCN, which drives the circadian rhythms of intracellular cAMP in the SCN. Furthermore, optical manipulation of intracellular cAMP levels in the SCN shifts molecular and behavioral circadian rhythms. Together, our study demonstrates that intracellular cAMP is a key molecule in the organization of the SCN circadian neuronal network.

RNA profiles reveal patterns of circadian rhythm in pregnancy

RNA profiles reveal patterns of circadian rhythm in pregnancy

INFLAMMATION MARKERS IN SUBJECTS WITH DIPPER AND NON-DIPPER BLOOD PRESSURE PATTERNS

Objective: Elevated inflammation markers play important role in vessels damage and remodeling in patients with hypertension. However, the data are limited concerning the association between blood pressure circadian rhythm and inflammation status, especially in early changes of a pattern of blood pressure circadian rhythm in normotensive subjects. The aim of the work was to study the connection between dipper and non-dipper patterns of blood pressure circadian variation and inflammatory markers in normotensive and hypertensive subjects. Design and method: The cross-sectional study included 125 hypertensive patients (54 men) with an age median of 56,5 [45.0 ÷ 63.7] years old and 41 normotensive subjects 52,1 [41.5 ÷ 61.2] years old. All hypertensive patients had been on stable antihypertensive therapy during the last three months and had target blood pressure at the moment of inclusion to the study. Ambulatory blood pressure monitoring was done to all patients with Heaco ABPM50 monitoring. Fasting glucose, blood lipids, creatinine, uric acid, high sensitive C-reactive protein (hCRP), and interleukin 1 beta (IL-1B) were measured. Physical activity was assessed using the International Physical Activity Questionnaire. Data were analyzed with SPSS IBM 19.0. Results: Parameters of ambulatory blood pressure monitoring are presented in the table1 1. Normotensive subjects had lower BMI than hypertensive patients (26,1 [23,5–28,4] vs 35,3 [31,0–37,9]), p = 0.03, Mann-Whitney). It was found out that hCRP was significantly higher in a non-dipper subgroup of hypertensive patients (7.43[3.26–11.45] vs 9.50[7.70–15.87], p = 0.01, Mann-Whitney) as well as in the non-dipper subgroup of normotensive patients (2.37[0.97–4.75] vs 2.87[1.84–523], p = 0,03, Mann-Whitney). There was no significant difference in interleukin-1b level in dipper and non-dipper normotensive patients (2.10 [1.63–2.65] vs 1.8 [1.55–2.10], p = 4.13, Mann-Whitney). However, in hypertensive patients with non-dipper patterns, interleukin-1b was significantly higher, than in dipper patients (2.21 [1.62–2.77] vs 2.26 [2.0–3.11], p = 0.03, Mann-Whitney). Conclusions: Non-dipper pattern of blood pressure circadian rhythm is associated with increased inflammatory markers in hypertensive patients as well as in normotensive subjects.

192-OR: T-Type Calcium Channel Cav3.2 in GABAergic Neurons Regulates Rhythmic Glucose Metabolism

Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking. The GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCNGABA neurons) were reported to control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice in earlier work1. SCNGABA neural firing activity displays a diurnal rhythm, with the intrinsic ionic mechanism underlying this temporal pattern not completely understood. Here we provided evidence supporting a role of the T type voltage-gated calcium ion channel subunit 3.2 (Cav3.2) in SCNGABA neurons in regulating rhythmic neural firing and glucose homeostasis. We found that Cav3.2 global knockout (Cav3.2KO) mice displayed disrupted diurnal rhythm of blood glucose levels. Selective deletion of Cav3.2 in the SCNGABA neurons abolished the oscillatory firing activity of SCNGABA neurons and led to glucose intolerance. Furthermore, our real-time calcium imaging data in freely moving mice showed that SCN GABA neuronal activity displayed a circadian rhythm pattern in WT control mice but not Cav3.2KO mice or mice with Cav3.2 selectively deleted in the SCNGABA neurons. These findings provide insights into how the calcium ion channel regulates the central circadian clock and glucose metabolism, with implications in the extended dawn phenomenon in type 2 diabetes. Keywords: Type 2 diabetes, calcium channel, Cav3.2, GABA neurons, circadian rhythm Reference: 1 Ding, G. et al. REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity. Nature 592, 763-767, doi:10.1038/s41586-021-03358-w (2021) . Disclosure P. Xu: None. W. Zhou: None. Z. Sun: None. Y. He: None. Funding NIH (P20 GM135002)