Nonphotic Zeitgebers Research Articles

Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review.

In mammals, the timing of physiological, biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms. To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm, environmental zeitgebers are used by the circadian system. This is done primarily by signals from the retina via the retinohypothalamic tract, but other cues like exercise, feeding, temperature, anxiety, and social events have also been shown to act as non-photic zeitgebers. The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise. Irisin is a product of cleavage and modification from its precursor membrane fibronectin type Ⅲ domain-containing protein 5 (FNDC5) in response to exercise. Apart from well-known peripheral effects, such as inducing the "browning" of white adipocytes, irisin can penetrate the blood-brain barrier and display the effects on the brain. Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions. In several brain areas, irisin induces the production of brain-derived neurotrophic factor (BDNF). In the master clock, a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested. However, the brain receptor for irisin remains unknown. In the current review, the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.

Effects of exercise on circadian rhythms in humans.

The biological clock system is an intrinsic timekeeping device that integrates internal physiology and external cues. Maintaining a healthy biological clock system is crucial for life. Disruptions to the body's internal clock can lead to disturbances in the sleep-wake cycle and abnormalities in hormone regulation, blood pressure, heart rate, and other vital processes. Long-term disturbances have been linked to the development of various common major diseases, including cardiovascular diseases, metabolic disorders, tumors, neuropsychiatric conditions, and so on. External factors, such as the diurnal rhythm of light, have a significant impact on the body's internal clock. Additionally, as an important non-photic zeitgeber, exercise can regulate the body's internal rhythms to a certain extent, making it possible to become a non-drug intervention for preventing and treating circadian rhythm disorders. This comprehensive review encompasses behavioral, physiological, and molecular perspectives to provide a deeper understanding of how exercise influences circadian rhythms and its association with related diseases.

Importance of mechanical cues in regulating musculoskeletal circadian clock rhythmicity: Implications for articular cartilage.

The circadian clock, a collection of endogenous cellular oscillators with an approximate 24-h cycle, involves autoregulatory transcriptional/translational feedback loops to enable synchronization within the body. Circadian rhythmicity is controlled by a master clock situated in the hypothalamus; however, peripheral tissues are also under the control of autonomous clocks which are coordinated by the master clock to regulate physiological processes. Although light is the primary signal required to entrain the body to the external day, non-photic zeitgeber including exercise also entrains circadian rhythmicity. Cellular mechano-sensing is imperative for functionality of physiological systems including musculoskeletal tissues. Over the last decade, mechano-regulation of circadian rhythmicity in skeletal muscle, intervertebral disc, and bone has been demonstrated to impact tissue homeostasis. In contrast, few publications exist characterizing the influence of mechanical loading on the circadian rhythm in articular cartilage, a musculoskeletal tissue in which loading is imperative for function; importantly, a dysregulated cartilage clock contributes to development of osteoarthritis. Hence, this review summarizes the literature on mechano-regulation of circadian clocks in musculoskeletal tissues and infers on their collective importance in understanding the circadian clock and its synchronicity for articular cartilage mechanobiology.

An increased number of individuals of a potential host facilitates non-photic synchronisation in the haematophagous insect Triatoma infestans.

Triatoma infestans (Kissing bug) is the main vector of the parasite causative of Chagas disease in Latin-America. This species shows clear activity rhythms easily synchronised to day-night cycles (photic cycle). The haematophagous nature of these insects lead us to think that they may temporally adapt to the particular activity rhythms of potential hosts (non-photic cycle). Our previous data showed that kissing bugs were weakly affected by the activity-inactivity rhythm of a single host. To determine if by increasing the number of individuals of a potential host, T. infestans could increase the likelihood of synchronisation. Individual activity rhythms of experimental insects, maintained in constant darkness in light-tight cabinets, localised in a room with 24 rodents, were continuously monitored. Another insect group that served as control was maintained in the same conditions but in a room without rodents. Most of the experimental insects synchronised, expressing a 24 h period coincident with the activity-inactivity rhythms of the rodents, while the controls free ran with a period significantly longer than 24 h. Analogous to what happens with high vs low light intensity in photic synchronisers, a high number of rodents, in contrast to the previous one-rodent experiment, increased the potency of this non-photic zeitgeber.

Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers.

Omega-3 fatty acids (ω-3 FAs) are well-known for their actions on immune/inflammatory and neurological pathways, functions that are also under circadian clock regulation. The daily photoperiod represents the primary circadian synchronizer (‘zeitgeber’), although diverse studies have pointed towards an influence of dietary FAs on the biological clock. A comprehensive literature review was conducted following predefined selection criteria with the aim of updating the evidence on the molecular mechanisms behind circadian rhythm regulation by ω-3 FAs. We collected preclinical and clinical studies, systematic reviews, and metanalyses focused on the effect of ω-3 FAs on circadian rhythms. Twenty animal (conducted on rodents and piglets) and human trials and one observational study providing evidence on the regulation of neurological, inflammatory/immune, metabolic, reproductive, cardiovascular, and biochemical processes by ω-3 FAs via clock genes were discussed. The evidence suggests that ω-3 FAs may serve as non-photic zeitgebers and prove therapeutically beneficial for circadian disruption-related pathologies. Future work should focus on the role of clock genes as a target for the therapeutic use of ω-3 FAs in inflammatory and neurological disorders, as well as on the bidirectional association between the molecular clock and ω-3 FAs.

Photic Entrainment of the Circadian System.

Circadian rhythms are essential for the survival of all organisms, enabling them to predict daily changes in the environment and time their behaviour appropriately. The molecular basis of such rhythms is the circadian clock, a self-sustaining molecular oscillator comprising a transcriptional–translational feedback loop. This must be continually readjusted to remain in alignment with the external world through a process termed entrainment, in which the phase of the master circadian clock in the suprachiasmatic nuclei (SCN) is adjusted in response to external time cues. In mammals, the primary time cue, or “zeitgeber”, is light, which inputs directly to the SCN where it is integrated with additional non-photic zeitgebers. The molecular mechanisms underlying photic entrainment are complex, comprising a number of regulatory factors. This review will outline the photoreception pathways mediating photic entrainment, and our current understanding of the molecular pathways that drive it in the SCN.

309 Food consumption and meal timing in hospital nurses with shift work: A preliminary study

Abstract Introduction One of the important nonphotic zeitgebers is food consumption. The timing of food consumption in relation to melatonin onset has been reported to be associated with fat proportion and BMI. Irregular meal timing along with irregular sleep schedules due to shift work would increase the metabolism problem as well as influencing sleep problems. The aim of the study is to evaluate the meal timing and food consumption in shift workers. Methods The nurses with 3-rapid rotating shifts were enrolled to keep food diaries for two weeks including all three shift schedules. They filled out a morningness-eveningness questionnaire. They wore actigraphy to monitor sleep-wake patterns with a daily sleep diary. The timing and the frequencies of meal/snack and caffeine consumption during each shift and day-off were reviewed. The calorie from each food was calculated depending on the nutritional information on the internet. Results 13 female nurses were screened and 6 finished the study. The mean age is 29.4±7.69 years and the mean body mass index was 20.2±1.1kg/m2. Average frequencies of meals are 2.59±0.49, 1.66±0.75, 1.93±0.41, 2.09±0.96 times per day, and average frequencies of snack consumption are 1.37±0.9, 1.07±0.74, 0.75±0.82, 0.96±0.79 times per day for the morning, evening, night, and the day off, respectively. Total calorie consumed are 1662.5±564.8, 1380.8 ± 940.3, 1596.8±838.1, 1505.8±706.9 kcals in the same order. Caffeine consumption was 0.29±0.46, 0.4±0.48, 0.72±0.65, 0.46±0.54 cups per day in the same order. One subject with morning type showed a relatively regular meal schedule throughout the shifts. The timing for main calorie consumption seemed to show delayed on evening and night shifts than morning shift although total calorie consumption was similar between each shift. Conclusion Although this is a preliminary study with a small number of subjects, it showed shift worker nurses have an inconsistent number of meals and calorie intake depending on their shifts. Caffeine consumption is very lower than expected. The subject with morning chronotype seemed to keep relatively regular meal timing throughout the shifts, suggesting chronotype influences meal timing in shift workers. Support (if any) This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2019R1A2C1090643).

Impact of Time-Restricted Feeding to Late Night on Adaptation to a 6 h Phase Advance of the Light-Dark Cycle in Mice.

In modern society, more and more people suffer from circadian disruption, which in turn affects health. But until now, there are no widely accepted therapies for circadian disorders. Rhythmic feeding behavior is one of the most potent non-photic zeitgebers, thus it has been suggested that it was important to eat during specific periods of time (time-restricted feeding, TRF) so that feeding is aligned with environmental cues under normal light/dark conditions. Here, we challenged mice with a 6 h advanced shift, combined with various approaches to TRF, and found that food restricted to the second half of the nights after the shift facilitated adaptation. This coincided with improved resilience to sepsis. These results raise the possibility of reducing the adverse responses to jet lag by subsequent timing of food intake.

Plasticity of Daily Behavioral Rhythms in Foragers and Nurses of the Ant Camponotus rufipes: Influence of Social Context and Feeding Times.

Daily activities within an ant colony need precise temporal organization, and an endogenous clock appears to be essential for such timing processes. A clock drives locomotor rhythms in isolated workers in a number of ant species, but its involvement in activities displayed in the social context is unknown. We compared locomotor rhythms in isolated individuals and behavioral rhythms in the social context of workers of the ant Camponotus rufipes. Both forager and nurse workers exhibited circadian rhythms in locomotor activity under constant conditions, indicating the involvement of an endogenous clock. Activity was mostly nocturnal and synchronized with the 12:12h light-dark-cycle. To evaluate whether rhythmicity was maintained in the social context and could be synchronized with non-photic zeitgebers such as feeding times, daily behavioral activities of single workers inside and outside the nest were quantified continuously over 24 hours in 1656 hours of video recordings. Food availability was limited to a short time window either at day or at night, thus mimicking natural conditions of temporally restricted food access. Most foragers showed circadian foraging behavior synchronized with food availability, either at day or nighttime. When isolated thereafter in single locomotor activity monitors, foragers mainly displayed arrhythmicity. Here, high mortality suggested potential stressful effects of the former restriction of food availability. In contrast, nurse workers showed high overall activity levels in the social context and performed their tasks all around the clock with no circadian pattern, likely to meet the needs of the brood. In isolation, the same individuals exhibited in turn strong rhythmic activity and nocturnality. Thus, endogenous activity rhythms were inhibited in the social context, and timing of daily behaviors was flexibly adapted to cope with task demands. As a similar socially-mediated plasticity in circadian rhythms was already shown in honey bees, the temporal organization in C. rufipes and honey bees appear to share similar basic features.

Melatonin Signal Transduction Pathways Require E-Box-Mediated Transcription of Per1 and Per2 to Reset the SCN Clock at Dusk.

Melatonin is released from the pineal gland into the circulatory system at night in the absence of light, acting as “hormone of darkness” to the brain and body. Melatonin also can regulate circadian phasing of the suprachiasmatic nucleus (SCN). During the day-to-night transition, melatonin exposure advances intrinsic SCN neural activity rhythms via the melatonin type-2 (MT2) receptor and downstream activation of protein kinase C (PKC). The effects of melatonin on SCN phasing have not been linked to daily changes in the expression of core genes that constitute the molecular framework of the circadian clock. Using real-time RT-PCR, we found that melatonin induces an increase in the expression of two clock genes, Period 1 (Per1) and Period 2 (Per2). This effect occurs at CT 10, when melatonin advances SCN phase, but not at CT 6, when it does not. Using anti-sense oligodeoxynucleotides (α ODNs) to Per 1 and Per 2, as well as to E-box enhancer sequences in the promoters of these genes, we show that their specific induction is necessary for the phase-altering effects of melatonin on SCN neural activity rhythms in the rat. These effects of melatonin on Per1 and Per2 were mediated by PKC. This is unlike day-active non-photic signals that reset the SCN clock by non-PCK signal transduction mechanisms and by decreasing Per1 expression. Rather, this finding extends roles for Per1 and Per2, which are critical to photic phase-resetting, to a nonphotic zeitgeber, melatonin, and suggest that the regulation of these clock gene transcripts is required for clock resetting by diverse regulatory cues.

Unique food-entrained circadian rhythm in cysteine414-alanine mutant mCRY1 transgenic mice.

Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Daily scheduled restricted feeding (RF), in which the food available time is restricted for several hours each day, elicits anticipatory activity. This food-anticipatory activity (FAA) is controlled by a food-entrainable oscillator (FEO) that is distinct from the suprachiasmatic nucleus (SCN), the master pacemaker in mammals. In an earlier report, we described generation of transgenic (Tg) mice ubiquitously overexpressing cysteine414-alanine mutant mCRY1. The Tg mice displayed long locomotor free-running periods (approximately 28 h) with rhythm splitting. Furthermore, their locomotor activity immediately re-adjusted to the advance of light–dark cycles (LD), suggesting some disorder in the coupling of SCN neurons. The present study examined the restricted feeding cycle (RF)-induced entrainment of locomotor activity in Tg mice in various light conditions. In LD, wild-type controls showed both FAA and LD-entrained activities. In Tg mice, almost all activity was eventually consolidated to a single bout before the feeding time. The result suggests a possibility that in Tg mice the feeding cycle dominates the LD cycle as an entrainment agent. In constant darkness (DD), wild-type mice exhibited robust free-run activity and FAA during RF. For Tg mice, only the rhythm entrained to RF was observed in DD. Furthermore, after returning to free feeding, the free-run started from the RF-entrained phase. These results suggest that the SCN of Tg mice is entrainable to RF and that the mCRY1 mutation alters the sensitivity of SCN to the cycle of nonphotic zeitgebers.Electronic supplementary materialThe online version of this article (doi:10.1007/s41105-016-0050-1) contains supplementary material, which is available to authorized users.

Pheromones as time cues for circadian rhythms in fish

Almost all living organisms, including fish, exhibit circadian rhythms. They synchronize their circadian clocks with the solar clock through the mediation of photic or non-photic zeitgebers. Pheromones are the major chemicals responsible for communication among the conspecifics. Pheromones are secreted by a sender and perceived by receiver (s), thus evoking a species specific response and in turn affecting the behavior of receiver (s). Can a pheromone act as a zeitgeber in fish? In this mini review attempts have been made to address the question.

Circadian locomotor activity and entrainment by light cycles in cave spiders (Dipluridae and Ctenidae) at the cave Los Riscos, Qro. México

Caves are a special environment in which to study the persistence of circadian rhythms in animals living in an apparent non cyclic environment. Diversity of animals from caves has been studied in order to detect circadian activity in different behaviors. This study reports that most spiders of the families Dipluridae and Ctenidae, found in the deepest and middle zones respectively of the Los Riscos cave, in Querétaro State, México, present circadian rhythms of locomotor activity in free running, and light-dark cycles induce a notable change in circadian period, suggesting an entraining of the locomotor activity rhythm. We discuss the existence of remnant circadian photoreceptors in a nonphotic environment, but also that nonphotic zeitgebers may entrain circadian activity of the fauna inside the cave.

Nicotinamide adenine dinucleotide: a possible circadian zeitgeber functioning in nontranscription oscillation

Emerging evidences have shown that circadian rhythm can also be regulated by a nontranscriptional mechanism. In this study, we investigated the in vitro rhythmic characters of peroxiredoxin2 (PRX2) and nicotinamide adenine dinucleotide (NAD) in red blood cells (RBCs) and/or in heparin anticoagulated plasma under different light conditions. Our results showed that NAD had a free-running rhythm in accordance with that of PRX2 in RBCs, and both rhythms were liable to light entrainment. A decreased expression of PRX2 in RBCs and a notable phase delay of locomotor activity were found in mice intravenously injected with NAD, suggesting that NAD in nontranscriptional oscillating systems could receive the light zeitgeber signal and influence the expression of PRX2. NAD may also act as a nonphotic zeitgeber, which could make an advanced phase shift of per2, entraining the transcriptional oscillating system to make these two oscillating systems synchronized in a very short time. This zeitgeber might be of great significance as a mediator between these two oscillating systems.

Endurance exercise modifies the circadian clock in zebrafish (Danio rerio) temperature independently

Several rodent and human studies revealed that physical exercise acts as a non-photic zeitgeber for the circadian clock. The intrinsic entraining mechanism is still unknown, although it was assumed that the exercise-mediated increase in core temperature could be the underlying zeitgeber. As the homoeostatic control of mammalian core temperature interferes strongly with the investigation of this hypothesis, the present study used the poikilotherm zebrafish to answer this question. Gene transcription levels of the two circadian core clock genes period1 and clock1 were quantified using real-time qPCR of whole animal zebrafish larvae. Long-term endurance exercise of zebrafish larvae aged 9-15 days post-fertilization (dpf) or 21-32 dpf at a constant water temperature of 25 °C caused significantly altered transcription levels of the circadian genes period1 and clock1. Cosinor analysis of diurnal transcription profiles obtained after 3 days of swim training revealed significant differences regarding acrophase, mesor and amplitude of period1, resulting in a phase delay of the gene oscillation. After termination of the exercise bout, at 15 dpf, oscillation amplitudes of both circadian genes were significantly reduced. The results showed that physical exercise is able to affect the transcription of circadian genes in developing zebrafish larvae. Considering the poikilothermy of zebrafish, an exercise-mediated change in body core temperature could be excluded as the underlying intrinsic zeitgeber. However, the day-active zebrafish arises as a useful model to address the synchronizing effect of exercise on the circadian clock.

Rest-Activity Cycle and Melatonin Rhythm in Blind Free-Runners Have Similar Periods

In the absence of the entraining light-dark cycle, most totally blind humans free-run, albeit with relative coordination to nonphotic zeitgebers. Such blind free-runners (BFRs) often attempt to maintain a 24-h sleep-wake schedule and consequently suffer from recurrent sleep disruption and daytime somnolence. This study was conducted to determine the periods of the free-running melatonin rhythm and of the rest-activity cycle in 16 BFRs. It was found that the non-24-h component of the rest-activity rhythm correlated with the observed period of the circadian pacemaker.

Enhancing Circadian Zeitgebers

THE LINK BETWEEN CIRCADIAN RHYTHMS AND SLEEP IS CLEARLY AN IMPORTANT ONE. THOSE OF US WHO STUDY THE EFFECTS OF AGING ON HUMAN circadian rhythms often seek to forge a link between the effects of aging on circadian rhythms (which most older persons and policy makers don't care about) and the effects of aging on sleep (which many older persons and policy makers do care about). Very often, the raison d'etre for the study of circadian rhythms in the aged (either explicitly stated or merely implied) is that such experiments might allow us to glean appropriate therapies for age-related circadian dysfunction. The hope is that by fixing older people's circadian rhythms we can fix their sleep, thus saving them from distress and, in some cases, inappropriately applied hypnotic medications. In this issue of SLEEP, Zisberg and colleagues1 present compelling evidence from a study of 89 Israeli seniors (both genders, mean age 75 y) to suggest that there are indeed certain circadian behaviors which may be associated with improved sleep. In particular, Zisberg, et al. used block multiple regression analyses to show that increased stability in daily routine (as measured by two separate instruments), predicted shorter sleep latency, higher sleep efficiency and increased overall sleep quality (using the Pittsburgh Sleep Quality Index).2 These effects were observed over and beyond those of functional status, comorbidities, and age. One instrument, the Scale of Older Adults' Routine (SOAR)3 involved three structured interviews spaced 2 weeks apart and yielded measures separately related to basic activities such as eating and sleeping, and to instrumental activities such as shopping and public transportation use. The other instrument, the Social Rhythm Metric (SRM)4 involved a prospective 2-week diary of the timing of five major daily events relating to sleep, meals and social contacts. Both instruments essentially yielded numbers representing the level of regularity of the individual's daily routine, and both were significantly correlated with self-rated sleep variables (and with each other). Circadian rhythms are driven by endogenous processes, are self-sustaining, and rely upon circadian time cues (zeitgebers) to remain appropriately oriented to the individual's environment and desired routine.5 The gold-standard measures of human circadian rhythms have been core body temperature and salivary or plasma melatonin levels. However, one can also make the case that the behavioral circadian rhythms related to the timing of sleep, meals, work and social interactions are just as valid circadian rhythms as the physiological ones. Moreover, these are the rhythms most salient to the individual himself or herself. The strength of behavioral circadian rhythms comprises the concept underlying the daily regularity scores, as measured by the SOAR and SRM in Zisberg et al.'s study(1). However, behavioral circadian rhythms are not only circadian rhythms in their own right, but also serve as gatekeepers to the zeitgebers that impinge on the individual and thus serve to entrain his/her circadian rhythms to a 24-h period. The most powerful of such zeitgebers are the photic ones resulting from sleeping in the dark, for example.5 There is, however, also evidence for non-photic zeitgebers such as exercise and social contacts.6 Thus the improved sleep observed by Zisberg et al.1 in seniors with a more regular daily lifestyle, may result both from the action of stronger behavioral circadian rhythms per se, and from those strong behavioral rhythms providing more coherent zeitgebers to the circadian system in general. Most behavioral treatments for insomnia7 include advice to the patient to be regular in their sleep timing (particularly in regard to rise-time), thus enhancing the strength of the patient's behavioral circadian rhythms. In both adults and college students, high SRM scores (greater daily regularity) have been shown to be associated with better subjective sleep.8,9 Perhaps more salient, though, is the issue of zeitgeber enhancement. A number of different studies10–12 have shown that enhancement of zeitgebers in elderly nursing home residents (e.g., by providing brighter light and/or daytime activities) can have beneficial effects on their sleep. Healthy seniors tend to have higher (i.e., more regular) lifestyles than do younger adults.13 In the auditory domain, those of us who work with the elderly often become accustomed to raising our voices slightly to accommodate their hearing loss. It may well be that seniors have found that a highly regular lifestyle has an equivalent effect in the circadian domain. By adopting a highly regular lifestyle it is possible that zeitgeber effects are amplified, perhaps accommodating age-related declines in endogenous circadian entrainment mechanisms. The Zisberg et al. findings1 raise the hope that simple behavioral therapies may, for some seniors, serve to improve their sleep. Future work needs to measure the physiological circadian rhythms and zeitgeber exposure of high- versus low-regularity seniors, in order to provide good theoretical underpinnings to such therapies.

Interspecific contact affects phase response and activity in Desert hamsters

Circadian rhythms enhance survival and reproductive fitness of animals by promoting optimal timing of behavior and physiology with reference to geophysical changes in environment. Although light is considered the dominant stimulus for entraining circadian rhythms, social stimuli can also act as zeitgebers. The aim of this study was to analyze how Desert hamsters ( Phodopus roborovskii) coordinate their behavior in time with that of animals of another competing species (Mongolian gerbils, Meriones unguiculatus). First, the behavior of hamsters was analyzed during a step-wise avoidance test. Two effects were observed: a) spatial separation if it was possible or b) shortening of the activity period due to contact without chance for avoidance. The latter finding was now further analyzed using a phase response curve (PRC). Here, phase shifts of Desert hamsters caused by single social interactions with Mongolian gerbils were quantified. Phase advances during the rest period were found at CT3 and CT9, a similar tendency was observed at CT6. A second phase advance was determined at CT18, coinciding with the end of the activity period. Then, it was tested whether additional activity during the stimulus was a trigger for the phase response. Although an increase in activity occurred especially when stimuli were applied during the rest period, there was no general relation between additional activity measured and the phase response shown. Overall, relevance of interspecific contact as nonphotic zeitgeber was indicated by phase shifts in a phase response curve. The shape of it can be explained by two behavioral adaptations; stress and contact avoidance.

Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression

The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2-3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression.

Breastfeeding, sleep and wake circadian rhythms show distinct temporal emerging patterns

The emerging patterns of breastfeeding, sleep and wake circadian rhythms in an infant and the breastfeeding emergence pattern of his elder sister are presented. Both children were raised under regular contact with photic and non-photic Zeitgebers. Data are related to the first four months of life of the infants, which correspond to the exclusive and ad libitum breastfeeding stage of their lives. Discrimination is made of “fasting-associated-wakefulness” (FAW) which is a wake state without feeding. Our data show that while FAW episodes are concentrated in the diurnal phase of the day since the first week of life, breastfeeding rhythm takes longer to show statistically significant circadian periodicity (four weeks) and to become monophasic, concentrated in the diurnal phase of the day (three/four months). This precedence of the consolidation of FAW rhythm indicates tight association between nocturnal sleep fragmentation and the drive to feed, in the first months of life of infants.