Search NASA⌕ Search

SEARCH · Search NASA

Results for “Circadian Regulation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2011

Molecular Mechanisms of Circadian Regulation During Spaceflight

Disruption of the regular environmental circadian cues in addition to stringent and demanding operational schedules are two main factors that undoubtedly impact sleep patterns and vigilant performance in the astronaut crews during spaceflight. Most research is focused on the behavioral aspects of the risk of circadian desynchronization, characterized by fatigue and health and performance decrement. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate this risk. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. The molecular clock consists of sets of proteins that perform different functions within the clock machinery: circadian oscillators (genes whose expression levels cycle during the day, keep the pass of cellular time and regulate downstream effector genes), the effector or output genes (those which impact the physiology of the tissue or organism), and the input genes (responsible for sensing the environmental cues that allow circadian entrainment). The main environmental cue is light. As opposed to the known photoreceptors (rods and cones), the non-visual light stimulus is received by a subset of the population of retinal ganglion cells called intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin (opsin 4 -Opn4-) as the photoreceptor. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight. To answer this question, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (animal enclosure module) mice were used as ground controls. Opn4 expression was analyzed by real time RT/qPCR and retinal sections were stained for Opn4 immunofluorescence. Opn4 was decreased (abrogated in one case) in retinas that concurrently showed higher evidence of oxidative stress. We propose that oxidative stress can lead to a decrease in melanopsin expression, likely via ipRGC loss or impairment, and thus, it can be a contributing factor to circadian disruption during spaceflight. Countermeasures contemplating the use of light should therefore be complemented with melanopsin expression maintenance and/or reduction in oxidative stress.

Zanello, Susana↗
NASA NTRS1999

Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

Review, Tutorial↗
NASA NTRS2012

Molecular Mechanisms of Circadian Regulation During Spaceflight

The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight.

Zanello, S. B.↗
NASA NTRS2003

Photic and circadian regulation of retinal melatonin in mammals

Several studies have established that melatonin synthesis occurs in the retina of vertebrates, including mammals. In mammals, a subpopulation of photoreceptors (probably the cones) synthesize melatonin. Melatonin synthesis in the retina is elevated at night and reduced during the day in a fashion similar to events in the pineal gland. Both the MT1 and MT2 melatonin receptors are present in the retina and retinal melatonin does not contribute to circulating levels, suggesting that retinal melatonin acts locally as a neurohormone and/or neuromodulator. Melatonin synthesis in the retina of mammals is under the control of a circadian oscillator, and circadian rhythms in melatonin synthesis and/or release have been described for several species of mammals. These rhythms are present in vivo, persist in vitro, are entrained by light and are temperature compensated. The cloning of the gene responsible for the synthesis of the enzyme arylalkylamine N-acetyltransferase (the key enzyme in the melatonin biosynthetic pathway) has allowed studies of the molecular mechanisms responsible for the generation of retinal melatonin rhythmicity. The present review focuses on the cellular and molecular mechanisms that regulate melatonin synthesis. In particular, we discuss how the photic environment and the circadian clock interact in determining melatonin levels, in addition to the role that melatonin plays in retinal physiology.

NASA Discipline Space Human Factors↗
NASA NTRS1994

Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight: Circadian Rhythms and Temperature Regulation - Part 1

Mammals have developed the ability to adapt to most variations encountered in their everyday environment. For example, homeotherms have developed the ability to maintain the internal cellular environment at a relatively constant temperature. Also, in order to compensate for temporal variations in the terrestrial environment, the circadian timing system has evolved. However, throughout the evolution of life on earth, living organisms have been exposed to the influence of an unvarying level of earth's gravity. As a result changes in gravity produce adaptive responses which are not completely understood. In particular, spaceflight has pronounced effects on various physiological and behavioral systems. Such systems include body temperature regulation and circadian rhythms. This program has examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite, COSMOS 2044, were exposed to 14 days of microgravity while constantly monitoring the circadian patterns temperature regulation, heart rate and activity. This experiment has extended our previous observations from COSMOS 1514, as well as providing insights into the physiological mechanisms that produce these changes.

Fuller, C. A.↗
NASA NTRS2002

Integration of human sleep-wake regulation and circadian rhythmicity

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

Review↗
NASA NTRS1999

Stability, precision, and near-24-hour period of the human circadian pacemaker

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

NASA Discipline Regulatory Physiology↗
NASA NTRS2002

Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection?

Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (T(b)), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in T(b) and an attenuated T(b) circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice (P < 0.0001). In contrast, the het mice did not exhibit a decrease in mean T(b) and only a slight decrease in T(b) circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

NASA Discipline Regulatory Physiology↗
NASA NTRS1998

Later endogenous circadian temperature nadir relative to an earlier wake time in older people

The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.

NASA Discipline Regulatory Physiology↗
NASA NTRS2017

Circadian and Fatigue Effects on the Dynamics of the Pupillary Light Reflex

The pupillary light reflex (PLR) is known to be driven by the photo-entrainment of intrinsically-photosensitive retinal ganglion cells. These ganglion cells are known to have retino-hypothalamic projections to the suprachiasmatic nuclei (SCN), which regulates circadian rhythms, and bilateral retinal projections to the pretectal area, which mediates the PLR (Dacey et al., 2005; Hattar et al., 2002, 2006). The magnitude of the PLR has previously been shown to show circadian variation (Mnch et al., 2012). In this study, we used a constant routine protocol (Mills et al., 1978) to examine circadian and fatigue effects on the dynamics of the PLR. We characterized the PLR (pupil size as a function of time) in response to a square-wave change in the luminance of a white display background, at ten different times over a single circadian cycle. Twelve subjects participated in three daytime baseline runs followed by 7 nighttime runs each separated by an hour (17 23 hours after awakening). The constriction and dilation phases of the PLR waveform were fit separately with a single exponential model (Longtin Milton, 1988; Milton Longtin, 1990) with time constants estimated using a least-squares method. The dilation time constant exhibited a distinct sinusoidal modulation across the circadian cycle and, after 23 hours of wakefulness, decreased on average by 82 ms (paired t-test, p 0.05) relative to baseline (mean: 543 ms). The constriction time constant however, did not show an overall decrease with increased wakefulness. We conclude that the dynamics of the PLR show circadian variation and that, in addition, the briskness of the dilation response to a step-decrease in luminance shows a homeostatic enhancement with increased wakefulness.

human performance↗
NASA NTRS2005

Cardiovascular tissues contain independent circadian clocks

Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

Non-NASA Center↗
NASA NTRS1980

Renal responses to central vascular expansion are suppressed at night in conscious primates

The renal and hemodynamic responses of squirrel monkeys to central vascular volume expansion induced by lower body positive pressure (LBPP) during the day and night are investigated. Twelve unanesthetized animals trained to sit in a metabolism chair in which they were restrained only at the waist by a partition separating upper and lower body chambers were subjected to 4 h of continuous LBPP during the day and night, and hemodynamic, urinary and drinking data were monitored. LBPP during day and night is found to induce similar increases in central venous pressure, rises in heart rate and elevations in mean arterial blood pressure. However, although daytime LBPP induced a significant increase in urine flow and sodium excretion, a marked nocturnal inhibition of the renal response to LBPP is observed. Analysis of the time course and circadian regulation patterns of the urinary responses suggests that several separate efferent control pathways are involved.

Kass, D. A.↗
NASA NTRS1994

Effects of light on brain and behavior

It is obvious that light entering the eye permits the sensory capacity of vision. The human species is highly dependent on visual perception of the environment and consequently, the scientific study of vision and visual mechanisms is a centuries old endeavor. Relatively new discoveries are now leading to an expanded understanding of the role of light entering the eye in addition to supporting vision, light has various nonvisual biological effects. Over the past thirty years, animal studies have shown that environmental light is the primary stimulus for regulating circadian rhythms, seasonal cycles, and neuroendocrine responses. As with all photobiological phenomena, the wavelength, intensity, timing and duration of a light stimulus is important in determining its regulatory influence on the circadian and neuroendocrine systems. Initially, the effects of light on rhythms and hormones were observed only in sub-human species. Research over the past decade, however, has confirmed that light entering the eyes of humans is a potent stimulus for controlling physiological rhythms. The aim of this paper is to examine three specific nonvisual responses in humans which are mediated by light entering the eye: light-induced melatonin suppression, light therapy for winter depression, and enhancement of nighttime performance. This will serve as a brief introduction to the growing database which demonstrates how light stimuli can influence physiology, mood and behavior in humans. Such information greatly expands our understanding of the human eye and will ultimately change our use of light in the human environment.

Brainard, George C.↗
NASA NTRS1996

Biological Rhythms and Temperature Regulation in Rhesus Monkeys During Spaceflight

This program examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite COSMOS 2229 were exposed to 11 2/3 days of microgravity. The circadian patterns temperature regulation, heart rate and activity were monitored constantly. This experiment has extended previous observations from COSMOS 1514 and 2044, as well as provided insights into the physiological mechanisms that produce these changes.

Fuller, Charles A.↗
NASA NTRS2021

Circadian Rhythms and Homeostatic Mechanisms for Sleep Regulation

This chapter examines circadian rhythms and homeostatic mechanisms for sleep regulation. It reviews the current evidence describing the two-process model of sleep regulation and how to assess disruption to either of these sleep drives. This chapter also reviews the role of the photic and non-photic resetting of the circadian rhythm and describes how some aspects of modern society can cause sleep and circadian disruption. Furthermore, this chapter describes how misalignment between the circadian rhythm and sleep homeostat, such as occurs during jet lag and shiftwork, can lead to sleep disruption. The short and long-term consequences of circadian misalignment are also reviewed.

Sleep↗
NASA NTRS2001

Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor

The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

Non-NASA Center↗
NASA NTRS2010

Photoreceptor System for Melatonin Regulation and Phototherapy

The present invention involves a light system for stimulating or regulating neuroendocrine, circadian, and photoneural systems in mammals based upon the discovery of peak sensitivity ranging from 425-505 nm; a light meter system for quantifying light which stimulates or regulates mammalian circadian, photoneural, and neuroendocrine systems. The present invention also relates to translucent and transparent materials, and lamps or other light sources with or without filters capable of stimulating or regulating neuroendocrine, circadian, and photoneural systems in mammals. Additionally, the present invention involves treatment of mammals with a wide variety of disorders or deficits, including light responsive disorders, eating disorders, menstrual cycle disorders, non-specific alerting and performance deficits, hormone-sensitive cancers, and cardiovascular disorders.

Brainard, George↗
NASA NTRS1994

Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight: Metabolism - Part 2

Energy expenditure can be regarded as the sum of two components; the basal metabolic rate and the energy costs of activity. Weight loss is usually associated with an energy deficit. A negative energy balance exists when energy intake is less that energy utilization. The deficit is made up by tissue catabolism (principally fat, but also some protein). By analyzing food and water intake, urine and fecal output, and changes in body weight, the Skylab investigators reached the unexpected conclusion that energy expenditure during spaceflight was about 5% greater than at 1 G (Leonard, 1983; Rambaut et al., 1977). Possible explanations for the human metabolic responses are an increased workload during spaceflight (Leonard, 1983), or as Rambaut and co-workers (1977) suggested, a progressive decrease in metabolic efficiency. It is likely to be very difficult to distinguish between these two possibilities in man because the activity component may be different during spaceflight than it is the ground. The problem is to measure energy expenditure with efficient precision during spaceflight in a non-invasive manner which will not interfere with other investigations or take an time. The doubly labeled water (DLW) method meets these criteria. The DLW method is the only method available for continuously measuring energy expenditure during spaceflight given the severely restricted conditions in the spaceflight environment. Therefore, this study focuses on the development and use of this procedure on nonhuman primates during spaceflight. Energy expenditure and total body water was determined in two Rhesus monkeys by the doubly labeled water (2H2'80) method. Three determinations were made. Monkey B (#2483) was studied twice, during the flight of COSMOS 2044 and during a follow-up ground control study a month later. A second monkey was studied on the ground only (Monkey D, #782).

Fuller, C. A.↗