Dynamical analysis of the effects of circadian clock on the neurotransmitter dopamine.

The circadian clock is an autonomous timing system that regulates the physiological and behavioral activities of organisms. Dopamine (DA) is an important neurotransmitter that is associated with many biological activities such as mood and movement. Experimental studies have shown that the circadian clock influences the DA system and disorders in the circadian clock lead to DA-related diseases. However, the regulatory mechanism of the circadian clock on DA is far from clear. In this paper, we apply an existing circadian-dopamine mathematical model to explore the effects of the circadian clock on DA. Based on numerical simulations, we find the disturbance of the circadian clock, including clock gene mutations, jet lag and light pulses, leads to abnormal DA levels. The effects of mutations in some clock genes on the mood and behavior of mice are closely related to DA disruptions. By sensitivity analysis of DA levels to parameter perturbation, we identify key reactions that affect DA levels, which provides insights into modulating DA disorders. Sudden changes in external light influence the circadian clock, bringing about effects on the DA system. Jet lag causes transient DA rhythm desynchronization with the environment and the influence of jet lag in different directions on DA level and phase varies. Light pulses affect the amplitude and phase shift of DA, which provides a promising method for treating DA disorders through light exposure. This study helps to better understand the impact of the circadian clock on the DA system and provides theoretical support for the treatment of DA disorders.

Effects of Long-Haul Travel on Recovery and Performance in Elite Athletes: A Systematic Review.

ABSTRACT: Rossiter, A, Warrington, GD, and Comyns, TM. Effects of long-haul travel on recovery and performance in elite athletes: a systematic review. J Strength Cond Res 36(11): 3234-3245, 2022-Elite athletes are often required to travel long-haul (LH) across numerous time zones for training or competition. However, the extent to which LH travel affects elite athlete performance remains largely unknown. The purpose of this systematic literature review was to critically evaluate available evidence on the effects of LH travel on elite athlete psychometric, physiological, sleep, and performance markers. Electronic database searches of PubMed, SPORTDiscus, Scopus, and Web of Science were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were eligible for inclusion if subjects were identified as elite athletes who embarked on a LH flight (>6 hours) and used an outcome measurement of recovery or performance after the flight. Studies that were retrospective, used light therapy or pharmacological interventions were not included. Of 2,719 records assessed, 14 studies comprising a total of 197 athletes from 6 sports met the inclusion criteria. There was an increase in perceived jet lag and disturbance to various physiological markers after LH travel; however, there was minimal disturbance in other psychometric markers. Sleep was not negatively affected by LH travel. Of 10 studies that assessed performance, 3 found decrements in indirect markers of performance. Elite athletes perceived themselves to be jet lagged and experienced disturbance to various physiological mechanisms after LH travel; however, the effect on performance was inconclusive. Future research would benefit from higher quality studies with improved control measures, larger sample sizes from a wider variety of sports, and use of ecologically valid measures of circadian rhythm and athletic performance.

Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag.

The suprachiasmatic nucleus (SCN) functions as the central pacemaker aligning physiological and behavioral oscillations to day/night (activity/inactivity) transitions. The light signal entrains the molecular clock of the photo-sensitive ventrolateral (VL) core of the SCN which in turn entrains the dorsomedial (DM) shell via the neurotransmitter vasoactive intestinal polypeptide (VIP). The shell converts the VIP rhythmic signals to circadian oscillations of arginine vasopressin (AVP), which eventually act as a neurotransmitter signal entraining the hypothalamic-pituitary-adrenal (HPA) axis, leading to robust circadian secretion of glucocorticoids. In this work, we discuss a semi-mechanistic mathematical model that reflects the essential hierarchical structure of the photic signal transduction from the SCN to the HPA axis. By incorporating the interactions across the core, the shell, and the HPA axis, we investigate how these coupled systems synchronize leading to robust circadian oscillations. Our model predicts the existence of personalized synchronization strategies that enable the maintenance of homeostatic rhythms while allowing for differential responses to transient and permanent light schedule changes. We simulated different behavioral situations leading to perturbed rhythmicity, performed a detailed computational analysis of the dynamic response of the system under varying light schedules, and determined that (1) significant interindividual diversity and flexibility characterize adaptation to varying light schedules; (2) an individual's tolerances to jet lag and alternating shift work are positively correlated, while the tolerances to jet lag and transient shift work are negatively correlated, which indicates trade-offs in an individual's ability to maintain physiological rhythmicity; (3) weak light sensitivity leads to the reduction of circadian flexibility, implying that light therapy can be a potential approach to address shift work and jet lag related disorders. Finally, we developed a map of the impact of the synchronization within the SCN and between the SCN and the HPA axis as it relates to the emergence of circadian flexibility.

Intervention for Reducing Sleep Disturbances After a 12-Time Zone Transition.

Hoshikawa, M, Uchida, S, and Dohi, M. Intervention for reducing sleep disturbances after a 12-time zone transition. J Strength Cond Res 34(7): 1803-1807, 2020-The purpose of this study was to examine the effect of an intervention consisting of bright light exposure, sleep schedule shifts, and ramelteon on sleep disturbances after a transition of 12 time zones. Two groups, which flew from Tokyo to Rio, participated in this study. The experimental group received the treatment, whereas the control group did not receive any treatment. The experimental group members were exposed to bright light at night and their sleep-wake schedules were gradually delayed for 4 days before their flight. They also took 8 mg of ramelteon once a day for 5 days from the day of their first flight. Both groups departed Tokyo at 14:05, transiting through Frankfurt and arriving in Rio at 05:05. In Rio, it was recommended that they go to bed earlier than usual if they experienced sleepiness. Nocturnal sleep variables measured by wristwatch actigraphy and subjective morning tiredness were compared between groups. Statistical analysis revealed shorter sleep onset latencies (SOLs) in the experimental group (p < 0.01). The SOLs in Rio were 7.7 ± 2.5 minutes for the experimental group and 16.3 ± 3.7 minutes for the control group (d = 0.89, effect size: large). Sleep efficiency for the first 3 nights in Rio was 88.5 ± 1.2% for the experimental group and 82.9 ± 3.0% for the control group (p < 0.01, d = 1.09, effect size: large). These results suggest that the intervention reduced sleep disturbances in Rio. Our intervention may increase the options for conditioning methods for athletic events requiring time zone transitions.

How to manage travel fatigue and jet lag in athletes? A systematic review of interventions.

OBJECTIVES: We investigated the management of travel fatigue and jet lag in athlete populations by evaluating studies that have applied non-pharmacological interventions (exercise, sleep, light and nutrition), and pharmacological interventions (melatonin, sedatives, stimulants, melatonin analogues, glucocorticoids and antihistamines) following long-haul transmeridian travel-based, or laboratory-based circadian system phase-shifts. DESIGN: Systematic review Eligibility criteria Randomised controlled trials (RCTs), and non-RCTs including experimental studies and observational studies, exploring interventions to manage travel fatigue and jet lag involving actual travel-based or laboratory-based phase-shifts. Studies included participants who were athletes, except for interventions rendering no athlete studies, then the search was expanded to include studies on healthy populations. DATA SOURCES: Electronic searches in PubMed, MEDLINE, CINAHL, Google Scholar and SPORTDiscus from inception to March 2019. We assessed included articles for risk of bias, methodological quality, level of evidence and quality of evidence. RESULTS: Twenty-two articles were included: 8 non-RCTs and 14 RCTs. No relevant travel fatigue papers were found. For jet lag, only 12 athlete-specific studies were available (six non-RCTs, six RCTs). In total (athletes and healthy populations), 11 non-pharmacological studies (participants 600; intervention group 290; four non-RCTs, seven RCTs) and 11 pharmacological studies (participants 1202; intervention group 870; four non-RCTs, seven RCTs) were included. For non-pharmacological interventions, seven studies across interventions related to actual travel and four to simulated travel. For pharmacological interventions, eight studies were based on actual travel and three on simulated travel. CONCLUSIONS: We found no literature pertaining to the management of travel fatigue. Evidence for the successful management of jet lag in athletes was of low quality. More field-based studies specifically on athlete populations are required with a multifaceted approach, better design and implementation to draw valid conclusions. PROSPERO registration number The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42019126852).

What works for jetlag? A systematic review of non-pharmacological interventions.

Jetlag is a combination of travel fatigue and circadian misalignment resulting from air travel across time zones. Routinely recommended interventions based on circadian science include timely exposure to light and darkness (scheduled sleep), but the real-world effectiveness of these and other non-circadian strategies is unknown. We systematically reviewed the evidence for non-pharmacological interventions for jetlag. PubMed, EMBASE, Scopus, and Web of Science were searched. Studies reviewed 1) involved human participants undergoing air travel with a corresponding shift in the external light-dark cycle; 2) administered a non-pharmacological intervention; 3) had a control or comparison group; and 4) examined outcomes such as jetlag symptoms, sleep, cognitive/physical performance, mood, fatigue, or circadian markers. Thirteen studies used light exposure, physical activity, diet, chiropractic treatment, or a multifaceted intervention to counteract jetlag. Nine studies found no significant change in the outcomes, three reported mixed findings, and one was positive. The null findings are likely due to poorly designed circadian interventions and neglect of contributors to travel fatigue. Higher quality studies that schedule darkness as well as light, in the periods before, during, and after flight are needed to reduce the circadian component of jetlag. Interventions should also address the stressors that contribute to travel fatigue.

[CME: Jet Lag Jetlag]. / CME: Jetlag CME-Fragen.

CME: Jet Lag Jetlag Abstract. Crossing several time zones by air travel leads to a temporary desynchronization of the internal clock with the external light/dark cycle. In the following jet lag occurs typically including difficulties falling asleep or waking up early as well as day-time sleepiness and significant reduction of wellbeing and fitness. To provide optimal medical advice, it is necessary to understand the human circadian rhythm and sleep-wake regulation. In consideration with additional information on travel plans, an approach to alleviate jet lag symptoms can be developed. This article addresses different supportive measures and advice on how to adjust to a new time zone and reduce jet lag symptoms.

Jetlag related sleep problems and their management: A review.

OBJECTIVES: We reviewed Jetlag, particularly in view of its effects on sleep and how it can be managed. METHODS: The Proquest Central database of Kirikkale University, PubMed and Google scholar were used while searching for the following key words: "Jetlag", "symptoms", "sleep", "melatonin" and "treatment". RESULTS: Flight dysrhythmia, otherwise known as jetlag, is caused by flying globally over various time zones. Most passengers who fly over six or more different time zones generally require 4-6 days after travelling to resume their usual sleep patterns and to feel less lethargic during the day. Signs of jet lag can vary between debilitated awareness, insomnia, feeling tired during the day and frequent waking during the night. During the night our pineal glands excrete a hormone called melatonin; dim lights cause the continuation of excretion of these hormones whereas any exposure to bright lights stems the flow of release. Common precautionary measures are specific diets, bright lights and melatonin agonists (Ramelteon, Agomelatine). CONCLUSION: Sleep issues derived from jetlag were found to be most common in passengers who flew through various time belts. Melatonin assumes a critical part in adjusting the body's circadian rhythms and has been utilized restoratively to re-establish irritated circadian rhythms.

Circadian Rhythm Sleep-Wake Disorders in Older Adults.

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows wakefulness throughout the day and a long consolidated sleep episode at night. Mismatch between the desired timing of sleep and the ability to fall and remain asleep is a hallmark of the circadian rhythm sleep-wake disorders. This article discusses changes in circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep-wake disorders; and how neurologic diseases in older patients affect circadian rhythms and sleep.

Jet Lag and Shift Work Disorder.

Jet lag and shift work disorder are circadian rhythm sleep-wake disorders resulting from behaviorally altering the sleep-wake schedule in relation to the external environment. Not everyone who experiences trans-meridian travel or performs shift work has a disorder. The prevalence of jet lag disorder is unclear, approximately 5%-10% of shift workers have shift work disorder. Treatment aims to realign the internal circadian clock with the external environment. Behavioral therapies include sleep hygiene and management of the light-dark and sleep schedule. Pharmacologic agents are used to treat insomnia and excessive sleepiness, and melatonin is used to facilitate sleep and circadian realignment.

Jet lag modification.

Athletes often are required to travel for sports participation, both for practice and competition. A number of those crossing multiple time zones will develop jet lag disorder with possible negative consequences on their performance. This review will discuss the etiology of jet lag disorder and the techniques that are available to shorten or minimize its effects. This includes both pharmacological and nonpharmacological approaches.

Effects of sleep hygiene and artificial bright light interventions on recovery from simulated international air travel.

PURPOSE: Despite the reported detrimental effects of international air travel on physical performance, a paucity of interventions have been scientifically tested and confirmed to benefit travelling athletes. Consequently, the aim of the present study was to examine the effects of sleep hygiene and artificial bright light interventions on physical performance following simulated international travel. METHODS: In a randomized crossover design, 13 physically active males completed 24 h of simulated international travel with (INT) and without (CON) the interventions. The mild hypoxia and cramped conditions typically encountered during commercial air travel were simulated in a normobaric, hypoxic room. Physical performance, subjective jet-lag symptoms and mood states were assessed in the morning and evening on the day prior to and for two days post-travel. Sleep quantity and quality were monitored throughout each trial. RESULTS: Sleep duration was significantly reduced during travel in both trials (P < 0.01), though total sleep duration during and following travel was almost significantly greater (P = 0.06) in INT (17.0 (16.2-17.8) h) compared to CON (15.7 (14.9-16.5) h). Maximal-sprint and countermovement jump (P < 0.05), but not Yo-Yo Intermittent Recovery level 1 test (P > 0.05) performance, were significantly reduced the evening of day 1 and 2 post-travel, with no differences between trials (P > 0.05). Furthermore, vigour was significantly greater (P = 0.04) the morning of day 2 in INT [5.3 (3.9-6.7)] compared to CON [2.8 (1.4-4.2)], and subjective jet-lag symptoms and mood states were significantly worse on day 2 in CON only (P < 0.05). CONCLUSIONS: Whilst reducing travel-induced sleep disruption may attenuate travel fatigue, no improvements in the recovery of physical performance were apparent.

Jet lag.

INTRODUCTION: Jet lag is a syndrome caused by disruption of the 'body clock', and affects most air travellers crossing five or more time zones; it is worse on eastward than on westward flights. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent or minimise jet lag? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found five studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: hypnotics, lifestyle and environmental adaptations, and melatonin.

Cell signaling, receptors, electrical effects and therapy in circadian rhythm.

Circadian rhythm has been the object of much attention. This review addresses the aspects of cell signaling, receptors, therapy and electrical effects in a multifaceted fashion. The pineal gland, which produces the important hormones melatonin and serotonin, exerts a prominent influence, in addition to the supraschiasmatic nucleus. Many aspects involve free radicals which have played a widespread role in biochemistry.

The times they're a-changing: effects of circadian desynchronization on physiology and disease.

Circadian rhythms are endogenous and need to be continuously entrained (synchronized) with the environment. Entrainment includes both coupling internal oscillators to external periodic changes as well as synchrony between the central clock and peripheral oscillators, which have been shown to exhibit different phases and resynchronization speed. Temporal desynchronization induces diverse physiological alterations that ultimately decrease quality of life and induces pathological situations. Indeed, there is a considerable amount of evidence regarding the deleterious effect of circadian dysfunction on overall health or on disease onset and progression, both in human studies and in animal models. In this review we discuss the general features of circadian entrainment and introduce diverse experimental models of desynchronization. In addition, we focus on metabolic, immune and cognitive alterations under situations of acute or chronic circadian desynchronization, as exemplified by jet-lag and shiftwork schedules. Moreover, such situations might lead to an enhanced susceptibility to diverse cancer types. Possible interventions (including light exposure, scheduled timing for meals and use of chronobiotics) are also discussed.

Circadian disruption and remedial interventions: effects and interventions for jet lag for athletic peak performance.

Jet lag has potentially serious deleterious effects on performance in athletes following transmeridian travel, where time zones are crossed eastwards or westwards; as such, travel causes specific effects related to desynchronization of the athlete's internal body clock or circadian clock. Athletes are particularly sensitive to the effects of jet lag, as many intrinsic aspects of sporting performance show a circadian rhythm, and optimum competitive results require all aspects of the athlete's mind and body to be working in tandem at their peak efficiency. International competition often requires transmeridian travel, and competition timings cannot be adjusted to suit individual athletes. It is therefore in the interest of the individual athlete and team to understand the effects of jet lag and the potential adaptation strategies that can be adopted. In this review, we describe the underlying genetic and physiological mechanisms controlling the circadian clock and its inherent ability to adapt to external conditions on a daily basis. We then examine the fundamentals of the various adaptation stimuli, such as light, chronobiotics (e.g. melatonin), exercise, and diet and meal timing, with particular emphasis on their suitability as strategies for competing athletes on the international circuit. These stimuli can be artificially manipulated to produce phase shifts in the circadian rhythm to promote adaptation in the optimum direction, but care must be taken to apply them at the correct time and dose, as the effects produced on the circadian rhythm follow a phase-response curve, with pronounced shifts in direction at different times. Light is the strongest realigning stimulus and careful timing of light exposure and avoidance can promote adjustment. Chronobiotics such as melatonin can also be used to realign the circadian clock but, as well as timing and dosage issues, there are also concerns as to its legal status in different countries and with the World Anti-Doping Agency. Experimental data concerning the effects of food intake and exercise timing on jet lag is limited to date in humans, and more research is required before firm guidelines can be stated. All these stimuli can also be used in pre-flight adaptation strategies to promote adjustment in the required direction, and implementation of these is described. In addition, the effects of individual variability at the behavioural and genetic levels are also discussed, along with the current limitations in assessment of these factors, and we then put forward three case studies, as examples of practical applications of these strategies, focusing on adaptations to travel involving competition in the Rugby Sevens World Cup and the 2016 Summer Olympics in Rio de Janeiro, Brazil. Finally, we provide a list of practice points for optimal adaptation of athletes to jet lag.

[Clinical picture and treatment of jet lag]. / Az idoeltolódás okozta tünetek (jet lag, "idozóna-baj") klinikai képe és kezelésének lehetoségei.

Symptoms associated with rapid time zone crosses represent one of the major health problems associated with commercial flights. This condition is termed jet lag that is characterized by sleep disturbances (insomnia, sleepiness), somatic symptoms, and decrease in mental and physical outputs. Difference between the light-darkness cycles of the destination and internal homeostatic rhythm is responsible for the syndrome. Restitution of the internal rhythm by appropriate light exposure or melatonin, optimal sleep time and duration, and drugs can be used in its treatment.

Jet lag and shift work sleep disorders: how to help reset the internal clock.

Jet lag sleep disorder and shift work sleep disorder are the result of dyssynchrony between the internal clock and the external light-dark cycle, brought on by rapid travel across time zones or by working a nonstandard schedule. Symptoms can be minimized by optimizing the sleep environment, by strategic avoidance of and exposure to light, and also with drug and behavioral therapies.