Circadian rhythms are self-sustained and adjustable cycles, typically entrained with light/dark and/or temperature cycles. These rhythms are present in animals, plants, fungi, and several bacteria. ...The central mechanism behind these “pacemakers” and the connection to the circadian regulated pathways are still poorly understood. The circadian rhythm of the cyanobacterium Synechococcus elongatus PCC 7942 (S. elongatus) is highly robust and controlled by only three proteins, KaiA, KaiB, and KaiC. This central clock system has been extensively studied functionally and structurally and can be reconstituted in vitro. These characteristics, together with a relatively small genome (2.7 Mbp), make S. elongatus an ideal model system for the study of circadian rhythms.
Different approaches have been used to reveal the influence of the central S. elongatus clock on rhythmic gene expression, rhythmic mRNA abundance, rhythmic DNA topology changes, and cell division. However, a global analysis of its proteome dynamics has not been reported yet.
To uncover the variation in protein abundances during 48 h under light and dark cycles (12:12 h), we used quantitative proteomics, with TMT 6-plex isobaric labeling. We queried the S. elongatus proteome at 10 different time points spanning a single 24-h period, leading to 20 time points over the full 48-h period.
Employing multidimensional separation and high-resolution mass spectrometry, we were able to find evidence for a total of 82% of the S. elongatus proteome. Of the 1537 proteins quantified over the time course of the experiment, only 77 underwent significant cyclic variations. Interestingly, our data provide evidence for in- and out-of-phase correlation between mRNA and protein levels for a set of specific genes and proteins. As a range of cyclic proteins are functionally not well annotated, this work provides a resource for further studies to explore the role of these proteins in the cyanobacterial circadian rhythm.
This paper reviews the evidence regarding the efficacy of behavioral treatments for bedtime problems and night wakings in young children. It is based on a review of 52 treatment studies by a task ...force appointed by the American Academy of Sleep Medicine to develop practice parameters on behavioral treatments for the clinical management of bedtime problems and night wakings in young children. The findings indicate that behavioral therapies produce reliable and durable changes. Across all studies, 94% report that behavioral interventions were efficacious, with over 80% of children treated demonstrating clinically significant improvement that was maintained for 3 to 6 months. In particular, empirical evidence from controlled group studies utilizing Sackett criteria for evidence-based treatment provides strong support for unmodified extinction and preventive parent education. In addition, support is provided for graduated extinction, bedtime fading/positive routines, and scheduled awakenings. Additional research is needed to examine delivery methods of treatment, longer-term efficacy, and the role of pharmacological agents. Furthermore, pediatric sleep researchers are strongly encouraged to develop standardized diagnostic criteria and more objective measures, and to come to a consensus on critical outcome variables.
The association between circadian rhythms and diseases has been well established, while the association with mental health is less explored. Given the heritable nature of circadian rhythms, this ...study aimed to investigate the relationship between genes underlying circadian rhythms and mental health outcomes, as well as a possible gene-environment correlation for circadian rhythms. Polygenic scores (PGSs) represent the genetic predisposition to develop a certain trait or disease. In a sample from the Netherlands Twin Register (N = 14,021), PGSs were calculated for two circadian rhythm measures: morningness and relative amplitude (RA). The PGSs were used to predict mental health outcomes such as subjective happiness, quality of life, and depressive symptoms. In addition, we performed the same prediction analysis in a within-family design in a subset of dizygotic twins. The PGS for morningness significantly predicted morningness (R2 = 1.55%) and depressive symptoms (R2 = 0.22%). The PGS for RA significantly predicted general health (R2 = 0.12%) and depressive symptoms (R2 = 0.20%). Item analysis of the depressive symptoms showed that 4 out of 14 items were significantly associated with the PGSs. Overall, the results showed that people with a genetic predisposition of being a morning person or with a high RA are likely to have fewer depressive symptoms. The four associated depressive symptoms described symptoms related to decision-making, energy, and feeling worthless or inferior, rather than sleep. Based on our findings future research should include a substantial role for circadian rhythms in depression research and should further explore the gene-environment correlation in circadian rhythms.
Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian ...rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation (“wake therapy”) can act within hours, and its mood‐elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first‐line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi‐centre trials, non‐reimbursement by medical insurance and their perceived difficulty or exotic “alternative” nature. Future use can be promoted by new technology (single‐sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non‐pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico‐limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi‐system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep‐related treatments of depression.
Artificial Light at Night (ALAN) threatens to disrupt most natural habitats and species, including those in coastal settings, where a growing number of studies have identified ALAN impacts. A careful ...examination of the light properties behind those impacts is important to better understand and manage the effects of this stressor. This study focused on ALAN monochromatic wavelengths and examined which types of light spectra altered the natural activity of two prominent coastal species from the Pacific southeast: the talitroid amphipod Orchestoidea tuberculata and the oniscoid isopod Tylos spinulosus. We compared the natural daylight/night activity of these organisms with the one they exhibit when exposed to five different ALAN wavelengths: lights in the violet, blue, green, amber, and red spectra. Our working hypothesis was that ALAN alters these species’ activity at night, but the magnitude of such impact differs depending on light wavelengths. Measurements of activity over 24 h cycles for five consecutive days and in three separate experiments confirmed a natural circadian activity pattern in both species, with strong activity at night (∼90% of probability) and barely any activity during daylight. However, when exposed to ALAN, activity declined significantly in both species under all light wavelengths. Interestingly, amphipods exhibited moderate activity (∼40% of probability) when exposed to red lights at night, whereas isopods shifted some of their activity to daylight hours in two of the experiments when exposed to blue or amber lights, suggesting a possible alteration in this species circadian rhythm. Altogether, our results were consistent with our working hypothesis, and suggest that ALAN reduces night activity, and some wavelengths have differential effects on each species. Differences between amphipods and isopods are likely related to their distinct adaptations to natural low-light habitat conditions, and therefore distinct sensitivity to ALAN.
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•Exposure to ALAN reduces the activity of sandy beach amphipods and isopods.•Evidence of a circadian rhythm shift was found in isopods in response to two spectra.•Peracarids' response to ALAN reveals photosensitivity variations between species.•Insight on light wavelengths may guide mitigation against coastal light pollution.
Abstract
Introduction:
In order to better understand the functions and origins of sleep, sleep should be studied across a variety of species. We aim to characterize sleep and wake in Acomys ...cahirinus, the Cairo spiny mouse. Few studies on the circadian activity of this species are available and nothing is known of their sleep behavior. Therefore, we have begun to characterize sleep, circadian rhythms, and eye closure for this species (A. cahirinus) in greater detail and alongside the well-studied house mouse (Mus musculus).
Methods:
Sleep and wake states were determined using a piezoelectric system for individually housed mice for 7 days under 12:12 LD condition. Four infrared cameras were set up around the cage to monitor activity patterns of A. cahirinus in light and dark conditions. Starting with one mouse, two more were added to the cage every four days ending with a total of five to study the effect of group housing on activity. Then, mice were surgically instrumented for tethered electroencephalogram (EEG) recording. To research eye closure of A. cahirinus, we set up a light flashing experiment to challenge the eye.
Results:
We found A. cahirinus and M. musculus to be primarily nocturnal, but with distinct behavioral patterns. The activity of A. cahirinus sharply increases at dark onset, but surprisingly, decreases sharply just one hour later. A. cahirinus is more active in the first half of the night than the second half in both single and group housing. Based on EEG analysis, A. cahirinus sleeps more than Mus during both day and night. The proportion of REM is significantly higher (nearly tripled). The proportion of wakefulness is more in the first half of the night. We also found that A. cahirinus do not close their eyes during sleep periods of the day or night, even with lights flashing.
Conclusion:
A. cahirinus has different sleep and circadian behavior than the standard laboratory nocturnal mouse. They sleep more than Mus during both daytime and night time. REM percentage is significantly higher.
Support (If Any):
NSF and OISE (IOS-1353713), NIH grant NS083218, Kentucky Cabinet for Economic Development.
Abstract
Introduction:
In humans and rodents, the timing of food consumption is a major contributor to body weight regulation. Sleep-wake cycle disruptions and circadian misalignment due to shifts ...from a diurnal to nocturnal lifestyle produce abnormal circadian rhythms and metabolic dysfunction. However, the metabolic consequences of a consistent, prolonged delayed eating pattern compared with a daytime one, are unknown.
Methods:
8 healthy adults (age: 26.25 ± 3.2y; BMI: 22.39 ± 1.9 kg/m2; 4 females) participated in a randomized cross-over study in free-living conditions with 2 phases: 1.) daytime eating (3 meals and 2 snacks consumed between 0800h-1900h); 2.) delayed eating (3 meals and 2 snacks consumed between 1200h-2300h). Energy and macronutrient content were comparable between conditions, and the sleep-wake cycle was held constant at 2300h-0700h (verified by actigraphy), with exercise levels controlled. Participants spent 8 weeks on the first condition, followed by a 2-week washout period, followed by 8 weeks on the second condition. Weight, adiposity, energy metabolism, and hormonal markers were assessed at 4 points: 1.) baseline; 2.) after the first eating condition; 3.) after the washout period, before the second eating condition began; and 4.) after the second eating condition. General Linear Models were used for statistical analysis, and cosinor analysis determined circadian rhythm amplitude and phase.
Results:
Preliminary analyses indicate delayed eating, compared to daytime eating, led to weight gain and increases in respiratory quotient. Insulin and cholesterol levels also were increased and adiponectin was decreased. In addition, the ghrelin phase was delayed with greater amplitude, while the melatonin phase and amplitude remained unchanged.
Conclusion:
This study provides the first experimental evidence that prolonged delayed eating promotes weight gain and a negative profile for fuel oxidation, energy metabolism and hormonal markers, in normal weight adults. Our findings suggest peripheral clocks may be affected by delayed timed eating, while the central clock remains entrained to the sleep-wake cycle.
Support (If Any):
This research was supported by NIH grant R21 DK100787.
Abstract
Introduction:
Circadian rhythm disruption is a prominent feature of numerous neurodegenerative, neurodevelopmental, and neuropsychiatric diseases that are also associated with verbal and ...physical aggression. However, whether the central circadian clock directly regulates aggression, a complex motivated behavior, and the circuit basis by which it may do so remains unknown. We hypothesized that the propensity towards aggressive behaviour varies across the 24 h day, and that the central circadian clock, located in the suprachiasmatic nucleus of the hypothalamus (SCN), regulates this rhythm. Estrogen receptor 1 (Esr1)-expressing neurons within the ventrolateral part of the ventromedial hypothalamus (VMHvl) are known to directly control attack behavior in male mice, but it is unknown if the activity of these neurons is under temporal regulation by the SCN clock. We thus hypothesized that circadian regulation of aggression may depend upon a polysynaptic pathway from the SCN to Esr1-expressing VMHvl neurons.
Methods:
We utilized the resident intruder paradigm (a well-established assay for territorial aggression in male mice) administered at four different circadian time points in conjunction with genetically-targeted neuronal manipulations focused on the GABAergic subparaventricular zone (SPZ), an obligate relay for most SCN clock synaptic output. We then used a series of channelrhodopsin assisted circuit mapping experiments to investigate functional connectivity between SCN, SPZ, and VMH neurons.
Results:
Here we demonstrate, for the first time, that aggression propensity in male mice exhibits a daily rhythm. We also found that this rhythm in aggression propensity requires normal functioning of SPZ GABA neurons and is independent of locomotor and plasma corticosterone rhythms. Finally, we uncovered a novel and functional polysynaptic circuit connecting the SCN clock with an intra-VMH circuit that, on activation, drives attack behavior.
Conclusion:
Our work reveals that aggression propensity exhibits a robust daily rhythm and that a circuit, spanning four synaptically coupled hypothalamic nodes, directly modulates this daily rhythm of aggression, primarily by inhibiting aggressive behavior in a circadian phase-dependent manner.
Support (If Any):
R01 NS072337 (CBS); F32 NS084582-01A1 (WDT).
Abstract
Introduction:
The circadian rhythm is an internal body cadence, responsible for regulation of sleep in all mammals. In humans, this clock is altered by several factors, including light and ...secretion of the hormone melatonin. Within the intensive care unit (ICU) population, it is well evidenced that patients suffer from circadian dysregulation, often for long periods of time.
Methods:
A prospective cohort pilot study of five subjects was undertaken to enable a greater understanding of sleep in medical ICU in Manitoba, Canada. From a total of thirty-six urine samples per subject, excretion of 6sulphatoxymelatonin (aMT6s), the urinary metabolite of melatonin was analyzed.
Results:
T-test comparison (p=0.05) of mean aMT6s (ng/mL) demonstrated significant differences in the nighttime excretion between subjects in this study and healthy individuals. No significant differences were observed when compared with mean aMT6s of ICU subjects in previous literature.
Conclusion:
Significant aberrancies in nighttime urinary melatonin excretion can be observed when compared to healthy individuals in adult medical ICU patients.
Support (If Any):
NA
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