Changes In Circadian Rhythms Research Articles

FRI375 Validation Of A Novel Mouse Placenta Explant Protocol For Screening Of Drugs Modulating Circadian Rhythms

Abstract Disclosure: J.S. Lee: None. H.M. Hoffmann: None. Introduction Pre-eclampsia is one of the leading causes of maternal, fetal, and neonatal morbidity and mortality, complicating about 4% of pregnancies. Recent work has identified PERIOD3 (PER3), a gene regulating 24-hour circadian rhythms, to be downregulated in the preeclamptic placenta. The role of circadian rhythms in the placenta largely remains unknown. Our goal is to establish an organotypic placental preparation to allow screening of drugs that regulate circadian rhythms. These studies are a first step towards understanding how circadian rhythm changes are caused in the placenta and will be the basis for future studies to understand how circadian rhythm disruption in the placenta cause pregnancy complications, such as preeclampsia. Methods We established a novel organotypic placenta preparation allowing to study circadian rhythms in a LumiCycle using gestation day (GD) 14 and GD18 placental explants from the validated circadian reporter mouse Per2::Luciferase. Using H&E we validated the explants to be >80% enriched in either decidua (DC) which is strictly of maternal origin, labyrinth (LB) which is strictly of fetal origin, and the junctional zone (JZ) which consists of binucleated cells fused of maternal and fetal cells. Results Through H&E staining, we validated by distinct morphology that the DC is enriched with neutrophils; the JZ contains spongiotrophoblasts and glycogen trophoblasts; whereas the LB has anucleated red blood cells. We next established a protocol to record Per2::Luciferase circadian rhythms for <6 days. We found that the Per2::Luciferase circadian rhythm shortens with increased gestational age, where the period in DC, LZ and LB in the GD14 placenta is ∼4h longer than in the GD18 placenta, showing an unexpected plasticity in circadian timekeeping in the placenta. Because PER3 is downregulated in the pre-eclamptic placenta, we asked if the explants would be useful for pharmacologically screenings. We applied PF670462 (1μM), which stabilizes PER1/2/3, or epidermal growth factor (EGF, 30ng/mL), a growth factor important in placental function and a PER2 enhancer. PF670462 lengthened Per2::Luciferase period in the DC and JZ, confirming the expected circadian rhythm stabilizing effect of PF670462. Surprisingly, EGF only modulated circadian rhythms in the GD14 placental, where EGF shortened Per2::Luciferase period in DC, and lengthen the period in the JZ and LB zones in the GD14 placenta. This data suggests EGF has gestational age and placenta zone specific effects. Conclusion We validated a novel ex vivo placental preparation to study circadian rhythms at GD14 and GD18. We identified a placenta zone and gestation age specific effect of EGF, an effect future studies will further expand on. This model will be useful to complete pharmacological screenings of drugs that can restore circadian rhythms in the preeclamptic placenta. Presentation: Friday, June 16, 2023

Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency

BackgroundSpinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic–adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear.Methods and objectivesThe concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic–adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine–immune network associated with SCI-IDS was further elucidated.ResultsThe spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses.ConclusionsTo explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

Intestinal microbial circadian rhythms drive sex differences in host immunity and metabolism

Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific intestinal microbial circadian rhythms in host metabolism using germ-free and conventionalized mice and manipulation of dietary-derived fat, fiber, and microbiota-accessible carbohydrates. Our findings demonstrate that sex differences in circadian rhythms of genes involved in immunity and metabolism depend on oscillations in microbiota, microbial metabolic functions, and microbial metabolites. Further, we show that consuming an obesogenic, high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. Our results reveal that microbial circadian rhythms contribute to sex differences in immunity and metabolism and that dietary factors can entrain new circadian rhythms and modify the magnitude of sex differences in host-microbe circadian dynamics.

The Effect of Lavender Aromatherapy to Improve the Sleep Quality of the Elderly at Tresna Werdha Abiyoso Social Service Center, Sleman

As part of aging or old age (elderly), general changes in circadian rhythms are referred to as earlier sleep phases. Prolonged sleep deprivation conditions can trigger many health system disorders, from a decrease in the body's immune system, weight gain due to uncontrolled appetite, and decreased level of concentration at work, to decreased patience and mood. One alternative non-pharmacological treatment to improve sleep quality is by providing lavender aromatherapy which will have a calming effect. This type of research is descriptive using a case study approach. A case study was conducted by applying non-pharmacological therapy with lavender aromatherapy to elderly respondents with sleep disorder nursing problems. The instruments used in this study were lavender aromatherapy, observation sheets, and sleep quality assessment sheets for the elderly. shows that there is an increase in the quality of sleep in the respondents. By doing this lavender aromatherapy therapy can help reduce sleep pattern disturbances in respondents. The results showed that there was an increase in sleep quality when patients could sleep soundly after being given lavender aromatherapy, so it can be concluded that there was an increase in sleep quality before and after giving lavender aromatherapy

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.

Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. Male mice received paroxetine (10mg/kg/day, s.c.) for 12days, then were swapped to saline injections for a 13day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.

Circadian Dysfunction in Adipose Tissue: Chronotherapy in Metabolic Diseases.

Essential for survival and reproduction, the circadian timing system (CTS) regulates adaptation to cyclical changes such as the light/dark cycle, temperature change, and food availability. The regulation of energy homeostasis possesses rhythmic properties that correspond to constantly fluctuating needs for energy production and consumption. Adipose tissue is mainly responsible for energy storage and, thus, operates as one of the principal components of energy homeostasis regulation. In accordance with its roles in energy homeostasis, alterations in adipose tissue's physiological processes are associated with numerous pathologies, such as obesity and type 2 diabetes. These alterations also include changes in circadian rhythm. In the current review, we aim to summarize the current knowledge regarding the circadian rhythmicity of adipogenesis, lipolysis, adipokine secretion, browning, and non-shivering thermogenesis in adipose tissue and to evaluate possible links between those alterations and metabolic diseases. Based on this evaluation, potential therapeutic approaches, as well as clock genes as potential therapeutic targets, are also discussed in the context of chronotherapy.

The association between cholesterol/saturated fat index (CSI) and quality of sleep, and circadian rhythm among overweight and obese women: a cross-sectional study

BackgroundThe decline in sleep quality is one of the main public health problems affecting the global population. Some studies have shown that a high-fat diet may be linked to changes in circadian rhythm and sleep quality. The cholesterol/saturated fatty acid index (CSI) determines the amount of cholesterol and saturated fatty acid (SFA) in people's dietary patterns and can affect the quality of sleep and circadian rhythm. However, to date, no studies have investigated the effect of this index on these two variables. Therefore, our aim was to investigate the relationship between CSI on circadian rhythm and sleep quality in obese and overweight women.MethodThis cross-sectional study included 378 adult women who were obese or overweight. Using accepted techniques, anthropometric measurements, blood pressure readings, and biochemical variables were evaluated. A validated and trustworthy semi-quantitative food frequency questionnaire (FFQ 147 items) was used to gauge dietary intake. The CSI was measured to find out how much cholesterol and saturated fats were in the diet. Additionally, to assess circadian rhythm and sleep quality, respectively, the valid morning-evening questionnaire (MEQ) and Pittsburgh sleep quality index (PSQI) questionnaires were utilized.ResultThe results of the multinomial logistic regression model of our analysis showed that a significant association was observed between circadian rhythm status with CSI score, and participants with one higher unit of CSI had a 7.3% more chance of being in the eveningness group than being in morningness category in the crude model (OR: 1.07; 95% CI 1.00, 1.14; P = 0.026). This association remains marginally significant when adjusting for age, energy intake, BMI, job status, thyroid, and smoking status (OR = 1.08; 95% CI 1.00, 1.16; P = 0.051). The binary logistic regression model showed that after controlling for potentially confounding variables, there was no significant association between sleep quality with CSI score, however, those with one higher unit of CSI had 1.6% more chance of having sleep problems (OR: 1.01; 95% CI 0.96, 1.06; P = 0.503).ConclusionOur results indicated a direct marginally significant association between CSI with evening type in overweight and obese women. Future studies are needed to clarify the precise link between circadian rhythm and sleep behavior with fatty acid quality index.

P15-006-23 Prevalence and Change in Circadian Rhythm Disrupting Sleep and Eating Behaviours in Breast Cancer Survivors Following a Weight Loss Intervention

P15-006-23 Prevalence and Change in Circadian Rhythm Disrupting Sleep and Eating Behaviours in Breast Cancer Survivors Following a Weight Loss Intervention

The gut-brain axis involved in polystyrene nanoplastics-induced neurotoxicity via reprogramming the circadian rhythm-related pathways

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 μg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

P-686 Long photoperiod exposure results in glycometabolism disorder in the cumulus-oocyte complex in SD rats

Abstract Study question Does long photoperiod exposure cause glycometabolism changes in the cumulus-oocyte complex? Summary answer The levels of key enzymes and substrates involved in glycometabolism have changed in the cumulus-oocyte complex in SD rats due to circadian rhythm changes. What is known already Circadian rhythm is essential for maintaining the required reproductive activities in mammalians. In our previous research, long photoperiod exposure results in the reduction of ovulation number and the increase of ROS level in oocytes. In the process of oocyte maturation, the tricarboxylic acid cycle and energy metabolism gradually increase, while the ability of the oocyte to absorb glucose is low. It is mainly metabolized by cumulus granulosa cells into pyruvate and then transported to oocytes for subsequent metabolism. Metabolomics is a comprehensive analysis of small molecules, which provides key information about cellular metabolic states. Study design, size, duration Female SD rats, 6-8 weeks old, were randomized into two groups. The rats (n = 20) were exposed to the control photoperiod (12 hours light/12 hours dark) or long photoperiod (16 hours light/8 hours dark) for 12 weeks. Participants/materials, setting, methods Cumulus-oocyte complexes were collected after ovarian stimulation and numbers were counted. The parameters compared include MII rate, fertilization rate, and ovarian follicle number. We used mass spectrometry-based metabolomics to directly measure metabolite abundance. The glycometabolism pathway and its regulatory signaling molecules were analyzed by qPCR and/or Western blots. Main results and the role of chance Long photoperiod exposure significantly reduced the ovulation rate, MII rate and fertilization rate. Interestingly, we find secondary follicle and antral follicle were decreased (p < 0.01), while primordial follicle and primary follicle were increased (p < 0.01). We identified a total of 318 metabolites in COC. Among them, 59 metabolite levels have significant differences between the two groups (FDR < 0.05). The metabolical function analysis suggested that the phosphatidylinositol phosphate metabolism, pyruvate metabolism, phosphatidylcholine biosynthesis, and glycolysis pathways were influenced by circadian interference. In addition, hexokinase, glucose-6-phosphate isomerase, phosphofructokinase glyceraldehyde 3-phosphate expression level were down regulated. Limitations, reasons for caution More studies are required to address how clock gene regulating glycometabolism process. And Translating results in rat model to the human setting is a limitation of this study. Wider implications of the findings Our study findings are first to demonstrate that glycolmetabolism is regulated by long photoperiod exposure in follicle development. This knowledge could help to develop strategies to modulate specific recovery strategies based on metabolic regulator to improve human IVF. Trial registration number Not applicable

Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression.

Intermittent hypoxia (IH) is a major clinical feature of obstructive sleep apnea (OSA). The mechanisms that become dysregulated after periods of exposure to IH are unclear, particularly in the early stages of disease. The circadian clock governs a wide array of biological functions and is intimately associated with stabilization of hypoxia-inducible factors (HIFs) under hypoxic conditions. In patients, IH occurs during the sleep phase of the 24-hour sleep-wake cycle, potentially affecting their circadian rhythms. Alterations in the circadian clock have the potential to accelerate pathological processes, including other comorbid conditions that can be associated with chronic, untreated OSA. We hypothesized that changes in the circadian clock would manifest differently in those organs and systems known to be impacted by OSA. Using an IH model to represent OSA, we evaluated circadian rhythmicity and mean 24-hour expression of the transcriptome in 6 different mouse tissues, including the liver, lung, kidney, muscle, heart, and cerebellum, after a 7-day exposure to IH. We found that transcriptomic changes within cardiopulmonary tissues were more affected by IH than other tissues. Also, IH exposure resulted in an overall increase in core body temperature. Our findings demonstrate a relationship between early exposure to IH and changes in specific physiological outcomes. This study provides insight into the early pathophysiological mechanisms associated with IH.

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< 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< 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.

Age-Related Changes in Circadian Rhythm and Association with Nutrition.

Considering the increase in life expectancy, there is a time-related decline in biological functions. Age-related changes are also observed in the circadian clock which directly leads to appropriate rhythms in the endocrine and metabolic pathways required for organism homeostasis. Circadian rhythms are affected by the sleep/wake cycle, environmental changes, and nutrition. The aim of this review is to show the relationship between age-related changes in circadian rhythms of physiological and molecular processes and nutritional differences in the elderly. Nutrition is an environmental factor that is particularly effective on peripheral clocks. Age-related physiological changes have an impact on nutrient intake and circadian processes. Considering the known effects of amino acid and energy intakes on peripheral and circadian clocks, it is thought that the change in circadian clocks in aging may occur due to anorexia due to physiological changes.

“Effect of time-restricted feeding on high-fat diet-induced metabolic dysfunction in Drosophila melanogaster”

BackgroundMetabolic alterations associated with obesity have been related to chronodisruption i.e., the desynchronization of molecular clocks that regulate circadian rhythms. The search for tools that improve the dietary treatment of obesity has recently focused on behaviors related to chronodisruption, and intermittent fasting is increasingly gaining interest. Studies in animal models have identified the benefits of time-restricted feeding (TRF) on metabolic alterations associated with changes in circadian rhythms induced by a high-fat diet. We aimed to evaluate the effect of TRF in flies with metabolic damage and chronodisruption. MethodsUsing high-fat diet fed Drosophila melanogaster as a model of metabolic damage and chronodisruption, we determined the impact of 12-h TRF on metabolic and molecular markers. Flies with metabolic dysfunction were switched to a control diet and randomly assigned to Ad libitum or a TRF regimen for seven days. We evaluated total triglyceride content, glycemia, weight, and 24 h mRNA expression rhythms of Nlaz (insulin resistance marker), clock genes (circadian rhythm molecular markers), and the neuropeptide Cch-amide2. ResultsFlies with metabolic damage that received TRF showed lower total triglyceride content, Nlaz expression, circulating glucose, and weight compared to Ad libitum. We observed the recovery of some of the high-fat diet-induced alterations in the amplitude of the circadian rhythm, particularly in the peripheral clock. ConclusionsTRF produced a partial reversal of metabolic dysfunction and chronodisruption of circadian cycles. General significanceTRF could be a useful tool to help to ameliorate metabolic and chronobiologic damage induced by a high-fat diet.

Metabolomic Analysis of Plasma in Huntington's Disease Transgenic Sheep (Ovis aries) Reveals Progressive Circadian Rhythm Dysregulation.

Metabolic abnormalities have long been predicted in Huntington's disease (HD) but remain poorly characterized. Chronobiological dysregulation has been described in HD and may include abnormalities in circadian-driven metabolism. Here we investigated metabolite profiles in the transgenic sheep model of HD (OVT73) at presymptomatic ages. Our goal was to understand changes to the metabolome as well as potential metabolite rhythm changes associated with HD. We used targeted liquid chromatography mass spectrometry (LC-MS) metabolomics to analyze metabolites in plasma samples taken from female HD transgenic and normal (control) sheep aged 5 and 7 years. Samples were taken hourly across a 27-h period. The resulting dataset was investigated by machine learning and chronobiological analysis. The metabolic profiles of HD and control sheep were separable by machine learning at both ages. We found both absolute and rhythmic differences in metabolites in HD compared to control sheep at 5 years of age. An increase in both the number of disturbed metabolites and the magnitude of change of acrophase (the time at which the rhythms peak) was seen in samples from 7-year-old HD compared to control sheep. There were striking similarities between the dysregulated metabolites identified in HD sheep and human patients (notably of phosphatidylcholines, amino acids, urea, and threonine). This work provides the first integrated analysis of changes in metabolism and circadian rhythmicity of metabolites in a large animal model of presymptomatic HD.

Personality Traits Interact With Sleep and Biological Rhythm in Patients With Bipolar Disorder.

Sleep disturbances and circadian rhythm changes in bipolar disorder (BD) may have behavioral components as well as biological components. This study aimed to examine the relationship between personality traits, sleep and circadian rhythm in BD. A total of 150 participants with BD, and 150 healthy controls completed the Big Five Personality Test-50 (B5PT-50-TR), Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN), Functioning Assessment Short Test (FAST), Pittsburgh Sleep Quality Index (PSQI), Young Mania Rating Scale and Beck Depression Inventory. In the BD group, B5PT-50-TR emotional stability and openness subscale scores were significantly lower in comparison with the healthy control group. Agreeableness and emotional stability subscales were covariates for the BRIAN sleep subscale and emotional stability was a covariate for PSQI total score. Emotional instability might be a vulnerability factor for sleep disorders and biological rhythm abnormalities in BD. Improvement in emotional instability may relieve sleep disorders and biological rhythm, thereby leading to better treatment outcomes in BD.

How Does Chronobiology Contribute to the Development of Diseases in Later Life.

An increasingly older population is one of the major social and medical challenges we currently face. Between 2010 and 2050, it is estimated that the proportion of adults over 65 years of age will double from 8% to 16% of the global population. A major concern associated with aging is the changes in health that can lead to various diseases such as cancer and neurogenerative diseases, which are major burdens on individuals and societies. Thus, it is imperative to better understand changes in sleep and circadian rhythms that accompany aging to improve the health of an older population and target diseases associated with aging. Circadian rhythms play a role in most physiological processes and can contribute to age-related diseases. Interestingly, there is a relationship between circadian rhythms and aging. For example, many older adults have a shift in chronotype, which is an individual's natural inclination to sleep certain times of the day. As adults age, most people tend to go to sleep earlier while also waking up earlier. Numerous studies also suggest that disrupted circadian rhythms may be indicative of developing age-related diseases, like neurodegenerative disorders and cancer. Better understanding the relationship between circadian rhythms and aging may allow us to improve current treatments or develop novel ones that target diseases commonly associated with aging.

Blepharospasm Patients after Botulinum Toxin - Sleep Approach.

Background Blepharospasm is a focal dystonia that affects the orbicularis oculi muscles. The interest in nonmotor symptoms is due to their impact on quality of life. Objective We evaluated the frequency of sleep disorders and circadian rhythm in a sample of Brazilian blepharospasm patients. Methods A total of 51 patients, who met the clinical criteria for blepharospasm, evaluated by 2 specialists in movement disorders, were recruited from the outpatient clinic for movement disorders of two reference centers in the city of São Paulo: Universidade Federal de São Paulo and Hospital do Servidor Público do Estado de São Paulo. The selected 13 patients were evaluated from 13 days before to 13 days after using botulinum toxin. They were interviewed, underwent physical examination and actigraphy, and completed sleep diaries. Results After using botulinum toxin, the group that reported sleep improvement exhibited a 50% decrease in sleep latency. There was no change in restless leg syndrome or circadian rhythm. Patients who reported no sleep improvement after using botulinum toxin presented poorer synchronization of the light-dark cycle. Conclusion Blepharospasm patients have poor sleep quality. About 50% of the patients had sleep improvement after using botulinum toxin. The synchronization of the light-dark cycle should be influenced by this finding.

Insights into the circadian rhythm alterations of the novel PFOS substitutes F-53B and OBS on adult zebrafish

As alternatives to perfluorooctane sulfonate (PFOS), 6:2 Cl-PFESA (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) are frequently detected in aquatic environments, but little is known about their neurotoxicity, especially in terms of circadian rhythms. In this study, adult zebrafish were chronically exposed to 1 μM PFOS, F-53B and OBS for 21 days taking circadian rhythm-dopamine (DA) regulatory network as an entry point to comparatively investigate their neurotoxicity and underlying mechanisms. The results showed that PFOS may affect the response to heat rather than circadian rhythms by reducing DA secretion due to disruption of calcium signaling pathway transduction caused by midbrain swelling. In contrast, F-53B and OBS altered the circadian rhythms of adult zebrafish, but their mechanisms of action were different. Specifically, F-53B might alter circadian rhythms by interfering with amino acid neurotransmitter metabolism and disrupting blood-brain barrier (BBB) formation, whereas OBS mainly inhibited canonical Wnt signaling transduction by reducing cilia formation in ependymal cells and induced midbrain ventriculomegaly, finally triggering imbalance in DA secretion and circadian rhythm changes. Our study highlights the need to focus on the environmental exposure risks of PFOS alternatives and the sequential and interactive mechanisms of their multiple toxicities.

Changes of adrenocorticotropic hormone rhythm and cortisol circadian rhythm in patients with depression complicated with anxiety and their effects on the psychological state of patients.

Objective: This work was to explore the rhythm of adrenocorticotropic hormone (ACTH) and cortisol in patients with depression and anxiety and their effects on mental state. In this work, with depression complicated with anxiety patients as the A-MDD group (n = 21), and depression without anxiety symptoms as the NA-MDD group (n = 21). Firstly, data features were extracted according to the electroencephalo-graph (EEG) data of different patients, and a DR model was constructed for diagnosis. The Hamilton Depression Scale 24 (HAMD-24) was employed to evaluate the severity, and the ACTH and cortisol levels were detected and compared for patients in the A-MDD group and NA-MDD group. In addition, the psychological status of the patients was assessed using the Toronto Alexithymia Scale (TAS). As a result, the AI-based DR model showed a high recognition accuracy for depression. The HAMD-24 score in the A-MDD group (31.81 ± 5.39 points) was statistically higher than the score in the NA-MDD group (25.25 ± 5.02 points) (P < 0.05). No visible difference was found in ACTH levels of patients in different groups (P > 0.05). The incidence of cortisol rhythm disorder (CRD) in the A-MDD group was much higher (P < 0.05). The differences in TAS scores between the two groups were significantly statistically significant (P < 0.01). In conclusion, the AI-based DR Model achieves a more accurate identification of depression; depression with or without anxiety has different effects on the mental state of patients. CRD may be one of the biological markers of depression combined with anxiety.