Entrainment Of Circadian Rhythms Research Articles

Melatonin ameliorates the sleep disorder induced by surgery under sevoflurane anaesthesia in aged mice.

Post-operative sleep disorders induce adverse effects on patients, especially the elderly, which may be associated with surgery and inhalational anaesthetics. Melatonin is a neuroendocrine regulator of the sleep-wake cycle. In this study, we analysed the alterations of post-operative sleep in aged melatonin-deficient (C57BL/6J) mice, and investigated if exogenous melatonin could facilitate entrainment of circadian rhythm after laparotomy under sevoflurane anaesthesia. The results showed that laparotomy under sevoflurane anaesthesia had a greater influence on post-operative sleep than sevoflurane alone. Laparotomy under anaesthesia led to circadian rhythm shifting forward, altered EEG power density and delta power of NREM sleep, and lengthened REM and NREM sleep latencies. In the light phase, the number of waking episodes tended to decline, and wake episode duration elevated. However, these indicators presented the opposite tendency during the dark phase. Melatonin showed significant efficacy for ameliorating the sleep disorder and restoring physiological sleep, and most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist.

Food Anticipatory Activity on Circadian Time Scales Is Not Dependent on Central Serotonin: Evidence From Tryptophan Hydroxylase-2 and Serotonin Transporter Knockout Mice.

A number of studies implicate biogenic amines in regulating circadian rhythms. In particular, dopamine and serotonin influence the entrainment of circadian rhythms to daily food availability. To study circadian entrainment to feeding, food availability is typically restricted to a short period within the light cycle daily. This results in a notable increase in pre-meal activity, termed “food anticipatory activity” (FAA), which typically develops within about 1 week of scheduled feeding. Several studies have implicated serotonin as a negative regulator of FAA: (1) aged rats treated with serotonin 5-HT2 and 3 receptor antagonists showed enhanced FAA, (2) mice lacking for the 2C serotonin receptor demonstrate enhanced FAA, and (3) pharmacologically increased serotonin levels suppressed FAA while decreased serotonin levels enhanced FAA in mice. We sought to confirm and extend these findings using genetic models with impairments in central serotonin production or re-uptake, but were surprised to find that both serotonin transporter (Slc6a4) and tryptophan hydroxylase-2 knockout mice demonstrated a normal behavioral response to timed, calorie restricted feeding. Our data suggest that FAA is largely independent of central serotonin and/or serotonin reuptake and that serotonin may not be a robust negative regulator of FAA.

Time-of-day affects the amount rats run during daily sessions in activity wheels.

When rats are given daily sessions of access to activity wheels, the amount that they run can increase over sessions. In addition to the suggestion that this could indicate the development of an addiction, there are alternative explanations. The present study tested whether running at a fixed time of day (ToD) might allow stronger entrainment of circadian rhythms than running at varied ToDs. In two experiments, Fixed groups of male rats were given 90-min wheel sessions at a fixed ToD during their dark period, while such sessions for Varied groups were given at times that varied over days between early in or in the middle of the dark period. In addition, each experiment also contained inactive controls in order to assess running-induced changes in body weight. Daily wheel sessions were given for 12 days in Experiment 1 and for 18 days in Experiment 2 to younger rats. In Experiment 1 the Fixed groups ran more each day, whereas little increase was found in the Varied groups. In Experiment 2 this difference was found only for rats in the Fixed condition whose sessions were held in the middle of the dark period. Independent of condition, rats ran more in the middle than early in the dark period. As previously reported, the rats given wheel access consumed less food and gained less weight than inactive rats. In conclusion, the results provided support for the proposal that wheel sessions at a fixed ToD entrain circadian rhythms and thus facilitate increases in running.

Conceptual Models of Entrainment, Jet Lag, and Seasonality.

Understanding entrainment of circadian rhythms is a central goal of chronobiology. Many factors, such as period, amplitude, Zeitgeber strength, and daylength, govern entrainment ranges and phases of entrainment. We have tested whether simple amplitude-phase models can provide insight into the control of entrainment phases. Using global optimization, we derived conceptual models with just three free parameters (period, amplitude, and relaxation rate) that reproduce known phenotypic features of vertebrate clocks: phase response curves (PRCs) with relatively small phase shifts, fast re-entrainment after jet lag, and seasonal variability to track light onset or offset. Since optimization found multiple sets of model parameters, we could study this model ensemble to gain insight into the underlying design principles. We found complex associations between model parameters and entrainment features. Arnold onions of representative models visualize strong dependencies of entrainment on periods, relative Zeitgeber strength, and photoperiods. Our results support the use of oscillator theory as a framework for understanding the entrainment of circadian clocks.

Colony Volatiles and Substrate-borne Vibrations Entrain Circadian Rhythms and Are Potential Cues Mediating Social Synchronization in Honey Bee Colonies.

Internal circadian clocks organize animal behavior and physiology and are entrained by ecologically relevant external time-givers such as light and temperature cycles. In the highly social honey bee, social time-givers are potent and can override photic entrainment, but the cues mediating social entrainment are unknown. Here, we tested whether substrate-borne vibrations and hive volatiles can mediate social synchronization in honey bees. We first placed newly emerged worker bees on the same or on a different substrate on which we placed cages with foragers entrained to ambient day-night cycles, while minimizing the spread of volatiles between cages. In the second experiment, we exposed young bees to constant airflow drawn from either a free-foraging colony or a similar-size control hive containing only heated empty honeycombs, while minimizing transfer of substrate-borne vibrations between cages. After 6 days, we isolated each focal bee in an individual cage in an environmental chamber and monitored her locomotor activity. We repeated each experiment 5 times, each trial with bees from a different source colony, monitoring a total of more than 1000 bees representing diverse genotypes. We found that bees placed on the same substrate as foragers showed a stronger phase coherence and a phase more similar to that of foragers compared with bees placed on a different substrate. In the second experiment, bees exposed to air drawn from a colony showed a stronger phase coherence and a phase more similar to that of foragers compared with bees exposed to air from an empty hive. These findings lend credence to the hypothesis that surrogates of activity entrain circadian rhythms and suggest that multiple social cues can act in concert to entrain social insect colonies to a common phase.

Temporal transcript abundance of clock genes, angiogenic factors and nutrient sensing genes in bovine placental explants

Recent research has shown expression of clock genes in peripheral tissue explants, targeting multiple pathways leading to the entrainment of circadian rhythms. Temporal variations are not solely regulated by photoperiod, but factors such as maternal feed availability can entrain fetal circadian clock. Currently, a paucity of information exists for clock gene expression and short-term temporal transcript abundance in the bovine placenta, which is essential for proper offspring development. Therefore, the objective of this study was to determine the effect of early to mid-gestational nutrient restriction on clock genes, angiogenic factors, and nutrient sensing genes mRNA transcript abundance in placental explants during a 24 h period. Placentomes from adequately fed and nutrient restricted heifers were collected via Cesarean section at day 180 of gestation; separated into caruncular and cotyledonary tissue and placed in culture media for a 24 h period. The mRNA transcript abundance of clock genes (ARNTL, CRY1, and PER2), angiogenic factors (HIF1A and VEGFA), and nutrient sensing genes (NAMPT and NR3C1) was determined every 4 h. Clock genes were expressed in caruncular and cotyledonary explant tissue. The caruncular explant transcript abundance of the clock genes was not influenced by time (P > 0.05); while ARNTL abundance decreased over time in the cotyledon explant (P < 0.05). A main effect of time was observed for HIF1A, VEGFA, and NR3C1 in the caruncular tissue (P < 0.05). Although, angiogenic factors and nutrient sensing genes in cotyledonary tissue displayed evident temporal variation in transcript abundance (P < 0.05). Nutrient restriction did not alter (P > 0.15) mRNA transcript abundance of clock genes, angiogenic factors, or nutrient sensing genes in either caruncular or cotyledonary tissue. Interestingly, these data may indicate limited transmission and synchronization of maternal and fetal temporal variations in transcript abundance. These findings demonstrate that multiple timepoint collections are needed in future studies due to the innate existence of temporal oscillations observed in the bovine placenta.

Light and Circadian Signaling Pathway in Pregnancy: Programming of Adult Health and Disease.

Light is a crucial environmental signal that affects elements of human health, including the entrainment of circadian rhythms. A suboptimal environment during pregnancy can increase the risk of offspring developing a wide range of chronic diseases in later life. Circadian rhythm disruption in pregnant women may have deleterious consequences for their progeny. In the modern world, maternal chronodisruption can be caused by shift work, jet travel across time zones, mistimed eating, and excessive artificial light exposure at night. However, the impact of maternal chronodisruption on the developmental programming of various chronic diseases remains largely unknown. In this review, we outline the impact of light, the circadian clock, and circadian signaling pathways in pregnancy and fetal development. Additionally, we show how to induce maternal chronodisruption in animal models, examine emerging research demonstrating long-term negative implications for offspring health following maternal chronodisruption, and summarize current evidence related to light and circadian signaling pathway targeted therapies in pregnancy to prevent the development of chronic diseases in offspring.

Circadian rhythms of sorting nexin 25 in the mouse suprachiasmatic nucleus

Entrainment of mammalian circadian rhythms requires receptor-mediated signaling in the hypothalamic suprachiasmatic nucleus (SCN), the site of the master circadian pacemaker. Receptor-mediated signaling is regulated by endocytosis, indicating that endocytosis-related proteins contribute to SCN pacemaking. Sorting nexin 25 (SNX25) belongs to the sorting nexin superfamily, whose members are responsible for membrane attachment to organelles of the endocytic system. In this study, we showed that Snx25 mRNA and SNX25 protein are highly expressed and exhibit remarkable circadian rhythms in the SCN of adult mice. Expression was maximal at about zeitgeber time (ZT) 16 in the subjective night and minimal at ZT8 in the subjective day. Prominent SNX25 immunoreactivity was found in the arginine vasopressin-positive neurons of the SCN. These findings suggest that SNX25 is a new actor in endocytic signaling, perhaps contributing to the circadian pacemaking system.

Behavioral and social routines and biological rhythms in prevention and treatment of pediatric obesity.

A growing body of research supports the potential importance of behavioral and social routines for children's health promotion and obesity risk reduction. Evidence in support of this comes from multiple lines of research, which suggest that specific behavioral routines, namely, eating and sleep routines, may be protective against excessive weight gain and development of pediatric obesity. Emerging work also supports the potential importance of the timing of these behavioral routines. From a circadian perspective, alignment of behavioral and social routines with underlying circadian rhythms may be particularly important for enhancing children's weight regulation. Specifically, engaging in appropriately timed behavioral routines may serve to entrain circadian rhythms that affect metabolism and weight regulation. Thus, in addition to promoting healthier eating, activity, and sleep behaviors for prevention and treatment of pediatric obesity, it may also be important to consider promotion of consistency in, and optimal timing of, these behaviors in an effort to enhance extant prevention and treatment approaches. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Mice Hypomorphic for &lt;i&gt;Pitx3&lt;/i&gt; Define a Minimal Dopamine Neuron Population Sufficient for Entraining Behavior and Metabolism to Scheduled Feeding

Pitx3ak mice lack a functioning retina and nearly all dopamine neurons of the substantia nigra (SN). del Rio-Marten et al (2019) reported that entrainment of circadian rhythms to daily light-dark and feeding schedules is absent in these mice. With food limited to 12h/day, food anticipatory circadian rhythms failed to emerge, and metabolic rhythms failed to synchronize with locomotor and feeding rhythms. The authors propose that retinal innervation of the suprachiasmatic nucleus clock is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms in Pitx3ak mice do not entrain to LD cycles, but we find no desynchrony between these rhythms nor a deficit in entrainment to daily feeding schedules. SN dopamine neurons surviving in Pitx3ak mice may define a mininum population sufficient for food entrainment.

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease.

Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD. We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

Sensing light without forming images

Human Retina In the rodent retina, intrinsically photosensitive retinal ganglion cells (ipRGCs) entrain circadian rhythms, modulate mood, and signal pupillary accommodation. Such responses are light-driven but not image-based. Working with donated human organ tissues, Mure et al. used electrophysiological approaches to identify ipRGCs in the human retina. The human retina has more cones than the retinas of nocturnal mice and rats. Differences in sensitivity, latency, and duration of responses identified three subtypes of human ipRGCs. Science , this issue p. [1251][1] [1]: /lookup/doi/10.1126/science.aaz0898

Functional diversity of human intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non-image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs' photoresponses. We discovered three functional ipRGC subtypes with distinct sensitivities and responses to light. The response of one ipRGC subtype appeared to depend on exogenous chromophore supply, and this response is conserved in both human and mouse retinas. Rods and cones also provided input to ipRGCs; however, each subtype integrated outer retina light signals in a distinct fashion.

Influence of the natural solar radiation in the mountains and artificial light on the circadian rhythms of motor activity

Light is the important zeitgeber in the entrainment of circadian rhythms. The aim of this researchis study the influence of the natural solar radiation with an increased proportion of short-wave light(short-term stay in the mountains) and the usual artificial light in urban conditions on circadian rhythmsof motor activity. The research involved healthy volunteers (N=12), aged 45 to 55 years, women, whoclimbed the ski resort “Shymbulak” during the experiment, as well as Alma-Arasan gorge and Big Almatylake as part of the usual tourist groups. For registration of motor activity used portable instruments registration of motor activity to configure a micro motion Logger (AMI), registered every minute ZCM, HPIM,PIM, light level. Package processing the primary data of programs Action 4 also includes a modifiedalgorithm for assessment of sleep-wakefulness. Circadian rhythms were evaluated on the basis of cosinoranalysis. Ecofitness have a significant stimulating effect on all chronostructural parameters of circadianrhythm of motor activity of both trained and untrained persons. In addition, Hiking in the mountains alsoaffects the duration of sleep, which should be taken into account in further studies of the influence ofmountains on the physiological state of the body of tourists and athletes.Key words: middle altitude, actigraphy, motor activity, sleep, light, chronostructure, tourist.

The inner clock-Blue light sets the human rhythm.

Visible light synchronizes the human biological clock in the suprachiasmatic nuclei of the hypothalamus to the solar 24‐hour cycle. Short wavelengths, perceived as blue color, are the strongest synchronizing agent for the circadian system that keeps most biological and psychological rhythms internally synchronized. Circadian rhythm is important for optimum function of organisms and circadian sleep–wake disruptions or chronic misalignment often may lead to psychiatric and neurodegenerative illness. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends not only on the light spectral composition but also on the timing of exposure and its intensity. Exposure to blue light during the day is important to suppress melatonin secretion, the hormone that is produced by the pineal gland and plays crucial role in circadian rhythm entrainment. While the exposure to blue is important for keeping organism's wellbeing, alertness, and cognitive performance during the day, chronic exposure to low‐intensity blue light directly before bedtime, may have serious implications on sleep quality, circadian phase and cycle durations. This rises inevitably the need for solutions to improve wellbeing, alertness, and cognitive performance in today's modern society where exposure to blue light emitting devices is ever increasing.

Focusing on the nuclear and subnuclear dynamics of light and circadian signalling.

Circadian clocks provide organisms the ability to synchronize their internal physiological responses with the external environment. This process, termed entrainment, occurs through the perception of internal and external stimuli. As with other organisms, in plants, the perception of light is a critical for the entrainment and sustainment of circadian rhythms. Red, blue, far-red, and UV-B light are perceived by the oscillator through the activity of photoreceptors. Four classes of photoreceptors signal to the oscillator: phytochromes, cryptochromes, UVR8, and LOV-KELCH domain proteins. In most cases, these photoreceptors localize to the nucleus in response to light and can associate to subnuclear structures to initiate downstream signalling. In this review, we will highlight the recent advances made in understanding the mechanisms facilitating the nuclear and subnuclear localization of photoreceptors and the role these subnuclear bodies have in photoreceptor signalling, including to the oscillator. We will also highlight recent progress that has been made in understanding the regulation of the nuclear and subnuclear localization of components of the plant circadian clock.

Splicing the Clock to Maintain and Entrain Circadian Rhythms.

Circadian clocks drive daily rhythms of physiology and behavior in multiple organisms and synchronize these rhythms to environmental cycles of light and temperature. The basic mechanism of the clock consists of a transcription-translation feedback loop, in which key clock proteins negatively regulate their own transcription. Although much of the focus with respect to clock mechanisms has been on the regulation of transcription and on the stability and activity of clock proteins, it is clear that other regulatory processes also have to be involved to explain aspects of clock function. Here, we review the role of alternative splicing in circadian clocks. Starting with a discussion of the Drosophila clock and then extending to other major circadian model systems, we describe how the control of alternative splicing enables organisms to maintain their circadian clocks as well as to respond to environmental inputs, in particular to temperature changes.

Type 1 equilibrative nucleoside transporter (ENT1) regulates sex-specific ethanol drinking during disruption of circadian rhythms.

Disruptions in circadian rhythms are risk factors for excessive alcohol drinking. The ethanol-sensitive adenosine equilibrative nucleoside transporter type 1 (ENT1, slc29a1) regulates ethanol-related behaviors, sleep, and entrainment of circadian rhythms. However, the mechanism underlying the increased ethanol consumption in ENT1 knockout (KO) mice in constant light (LL) and whether there are sex differences in ethanol consumption in ENT1 mice are less studied. Here, we investigated the effects of loss of ENT1, LL, and sex on ethanol drinking using two-bottle choice. In addition, we monitored the locomotor activity rhythms. We found that LL increased ethanol drinking and reduced accumbal ENT1 expression and adenosine levels in male but not female mice, compared with control mice. Interestingly, only LL-exposed male, not female, ENT1 KO mice exhibited higher ethanol drinking and a longer circadian period with a higher amplitude compared with wild-type (WT) mice. Furthermore, viral-mediated rescue of ENT1 expression in the NAc of ENT1 KO mice reduced ethanol drinking, demonstrating a possible causal link between ENT1 expression and ethanol drinking in males. Together, our findings indicate that deficiency of ENT1 expression contributes to excessive ethanol drinking in a sex-dependent manner.

Affectations in photic and thermic circadian entrainment of the locomotor activity rhythm in obese volcano mouse Neotomodon alstoni

ABSTRACT Obesity affects the ability of both photic and non-photic entrainment of the locomotor activity's circadian rhythm in the volcano mouse Neotomodon alstoni. The present study aimed to recognize differences in the synchronization of semi-natural, artificial, and periods other than 24 h light cycles between lean and obese mice. Also, the entrainment to temperature cycles was explored. The results obtained indicate that the activity profiles show discrete differences in the amplitude according to the type of lighting; when exposed to 22 or 26 h photic cycles, obese mice manifest more difficulty in the entrainment of the circadian rhythm. Changes in the free-running period produced by temperature cycles were larger in lean mice than in obese mice, with variability among organisms. The above confirms that photic entrainment is more difficult in obese mice, and that temperature entrainment suggest a decreased sensibility to temperature cycles in obese mice.

Impact of Diabetic Retinopathy on Sleep, Mood, and Quality of Life.

PurposeDiabetic retinopathy (DR) is associated with retinal neuronal and vascular damage. DR has previously been shown to affect the photosensitive retinal ganglion cells (pRGCs). PRGCs are essential for the entrainment of circadian rhythms; thus, DR progression could lead to worsening sleep quality and mood. We investigate the relationship between increasing DR severity, and its impact on sleep quality and mood.MethodsA total of 430 participants with DR, and 303 healthy controls with no ocular disease or preexisting sleep disorders were recruited. DR severity was grouped as follows: 1, mild nonproliferative (NPDR); 2, moderate/severe NPDR; and 3, proliferative diabetic retinopathy (PDR). Sleep, mood, and quality of life were assessed using the Pittsburgh Sleep Quality Index (PSQI), quality of life (SF-36), and Hospital Anxiety and Depression Score (HADS) questionnaires. Data were analyzed by severity of DR, and correlated with sleep, QOL, and mood and compared to controls.ResultsNo significant difference between PSQI scores in the DR group or the control group was identified despite severity of DR. Mean anxiety and depression scores were within the normal range for both groups. Despite a lower general health and physical function, the DR group had lower anxiety scores than controls.ConclusionsThese data show that even in severe DR, sleep quality is similar to controls. However, this could be explained by the majority of individuals in this study having good visual acuities in the better eye with a residual population of pRGCs remaining unaffected by DR.