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At least 163 records · Page 9

Significance of light and social cues in the maintenance of temporal organization in man

The effects of light:darkness (LD) cycles and social interaction on the response to long-term confinement (105 days) were investigated experimentally in three groups of three male subjects aged 20-24 years. Data from measurements of physiological parameters indicating changes in circadian rhythms are presented in graphs and analyzed; it is found that the LD-induced rhythm changes observed in previous studies of subjects isolated singly do not appear when subjects are confined in groups of three, suggesting a positive adaptive effect of social contact. In one subject who was transferred to a different group at day 84, hostile social interactions and poor circadian-rhythm entrainment were observed; the possible reasons for this response are considered.

Winget, C. M.↗

The biological clock of Neurospora in a microgravity environment

The effects of simulated microgravity (via the use of a slowly rotating clinostat), altered orientation (via alterations in the vector of a 1-g force), and hypergravity (via centrifugation) on the circadian rhythm of conidiation in Neurospora crassa were investigated. It was found that the clinostat, while capable of producing some of the microgravity effects seen in space (Sulzman, 1984), did not produce major repeatable results. Similarly, alterations of the vector of a 1-g gravity load were not adequate simulations of space flight on the conidiation rhythm. The results on the acute and chronic exposures to hypergravity demonstrated that chronic exposure of Neurospora to a 3-g force had no damping effect. On the other hand, an acute 10-min exposure to this hypergravity (the lift-off conditions) was found to cause significant damping on the circadian rhythm of conidiation. This effect was eliminated by a brief light pulse given 36 hrs after the exposure to 3 g.

Ferraro, James S.↗

Light as a chronobiologic countermeasure for long-duration space operations

Long-duration space missions require adaptation to work-rest schedules which are substantially shifted with respect to earth. Astronauts are expected to work in two-shift operations and the environmental synchronizers (zeitgebers) in a spacecraft differ significantly from those on earth. A study on circadian rhythms, sleep, and performance was conducted by exposing four subjects to 6 deg head-down tilt bedrest (to simulate the effects of the weightless condition) and imposing a 12-h shift (6 h delay per day for two days). Bright light was tested in a cross-over design as a countermeasure for achieving faster resynchronization and regaining stable conditions for sleep and circadian rhythmicity. Data collection included objective sleep recording, temperature, heart rate, and excretion of hormones and electrolytes as well as performance and responses to questionnaires. Even without a shift in the sleep-wake cycle, the sleep quantity, circadian amplitudes and 24 h means decreased in many functions under bedrest conditions. During the shift days, sleepiness and fatigue increased, and alertness decreased. However, sleep quantity was regained, and resynchronization was completed within seven days after the shift for almost all functions, irrespective of whether light was administered during day-time or night-time hours. The time of day of light exposure surprisingly appeared not to have a discriminatory effect on the resynchronization speed under shift and bedrest conditions. The results indicate that simulated weightlessness alters circadian rhythms and sleep, and that schedule changes induce additional physiological disruption with decreased subjective alertness and increased fatigue. Because of their operational implications, these phenomena deserve additional investigation.

Samel, Alexander↗

Influence of gravity on the circadian timing system

The circadian timing system (CTS) is responsible for daily temporal coordination of physiological and behavioral functions both internally and with the external environment. Experiments in altered gravitational environments have revealed changes in circadian rhythms of species ranging from fungi to primates. The altered gravitational environments examined included both the microgravity environment of spaceflight and hyperdynamic environments produced by centrifugation. Acute exposure to altered gravitational environments changed homeostatic parameters such as body temperature. These changes were time of day dependent. Exposure to gravitational alterations of relatively short duration produced changes in both the homeostatic level and the amplitude of circadian rhythms. Chronic exposure to a non-earth level of gravity resulted in changes in the period of the expressed rhythms as well as in the phase relationships between the rhythms and between the rhythms and the external environment. In addition, alterations in gravity appeared to act as a time cue for the CTS. Altered gravity also affected the sensitivity of the pacemaker to other aspects of the environment (i.e., light) and to shifts of time cues. Taken together, these studies lead to the conclusion that the CTS is indeed sensitive to gravity and its alterations. This finding has implications for both basic biology and space medicine.

Fuller, C. A.↗

Loss of circadian rhythmicity in body temperature and locomotor activity following suprachiasmatic lesions in the rat

In experiments on male and female ambulatory rats, the effect of bilateral suprachiasmatic lesions on deep body temperature and locomotor activity circadian rhythms was investigated. A L/D:12/12 cycle and 23 C ambient temperature were maintained. One-half of the rats received radiofrequency lesions in the suprachiasmic nucleus (SCN) while the second group were sham operated by lowering the radiofrequency electrode to the SCN without producing electrolytic lesions. Four weeks were allowed for recuperation. Autopsies were conducted to make sure that the lesions were restricted to SCN. The results show the complete disappearance of circadian rhythm in the SCN lesioned rats and only a slight diminution for the sham operated rats.

Saleh, M. A.↗

Immune System Dysregulation and Latent Herpesvirus Reactivation During Winterover at Concordia Station, Dome C, Antarctica

Immune system dysregulation occurs during spaceflight and consists of altered peripheral leukocyte distribution, reductions in immunocyte function and altered cytokine production profiles. Causes may include stress, confinement, isolation, and disrupted circadian rhythms. All of these factors may be replicated to some degree in terrestrial environments. NASA is currently evaluating the potential for a ground-based analog for immune dysregulation, which would have utility for mechanistic investigations and countermeasures evaluation. For ground-based space physiology research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over, consisting of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation and disrupted circadian rhythms, is potentially a good ground-analog for spaceflight-associated immune dysregulation. Of all Antarctica bases, the French-Italian Concordia Station, may be the most appropriate to replicate spaceflight/exploration conditions. Concordia is an interior base located in harsh environmental conditions, and has been constructed to house small, international crews in a station-environment similar to what should be experienced by deep space astronauts. The ESA-NASA CHOICE study assessed innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. The study was conducted over two winterover missions in 2009 and 2010. Final study data from NASA participation in these missions will be presented.

Crucian, B. E.↗

Circadian variation of intercompartmental potassium fluxes in man

Circadian rhythms of plasma potassium concentration and urinary potassium excretion persisted in three normal volunteers when diurnal variations in activity, posture, and dietary intake were eliminated for 3-10 days. Measurements of the arteriovenous difference in plasma potassium concentration across the resting forearm and of erythrocyte potassium concentration suggested that there is a net flux of potassium from ICF to ECF in the early morning and a reverse net flux later in the day. The total net ICF-ECF fluxes were estimated from the diurnal variations in extracellular potassium content corrected for dietary intake and urinary potassium loss. The net fluxes between ICF and ECF were found to be counterbalanced by the circadian rhythm in urinary potassium excretion. Desynchronization of these rhythms would result in marked fluctuations in extracellular potassium content. These findings suggest that some revision is required of the concept of basal state in potassium homeostasis.

Moore Ede, M. C.↗

The ESA-NASA CHOICE Study: Winterover at Concordia Station, Interior Antarctica, A Potential Analog for Spaceflight-Associated Immune Dysregulation

For ground-based space physiological research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over at the European Concordia Station is potentially a superior ground-analog for spaceflight-associated immune dysregulation (SAID). Concordia missions consist of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation, disrupted circadian rhythms and international crews. The ESA-NASA CHOICE study assesses innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. Initial data obtained from the first study deployment (2009 mission; 'n' of 6) will be presented, and logistical challenges regarding analog usage for biological studies will also be discussed. The total WBC increased, and alterations in some peripheral leukocyte populations were observed during winterover at Concordia Station. Percentages of lymphocytes and monocytes increased, and levels of senescent CD8+ T cells were increased during deployment. Transient increases in constitutively activated T cell subsets were observed, at mission time points associated with endemic disease outbreaks. T cell function (early blastogenesis response) was increased near the entry/exit deployment phases, and production of most measured cytokines increased during deployment. Salivary cortisol demonstrated high variability during winterover, but was generally increased. A 2-point circadian rhythm of cortisol measurement (morning/evening) was unaltered during winterover. Perceived stress was mildly elevated during winterover. Other measures, including in-vitro DTH assessment, viral specific T cell number/function and latent herpesvirus reactivation have not yet been completed for the 2009 winterover subjects. Based on the preliminary data, alterations in immune cell distribution and function appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Based on the initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune changes.

Crucian, B. E.↗

Light-Induced Alterations in Striatal Neurochemical Profiles

Much of our present knowledge regarding circadian rhythms and biological activity during space flight has been derived from those missions orbiting the Earth. During space missions, astronauts can become exposed to bright/dark cycles that vary considerably from those that entrain the mammalian biological timing system to the 24-hour cycle found on Earth. As a spacecraft orbits the Earth, the duration of the light/dark period experienced becomes a function of the time it takes to circumnavigate the planet which in turn depends upon the altitude of the craft. Orbiting the Earth at an altitude of 200-800 km provides a light/dark cycle lasting between 80 and 140 minutes, whereas a voyage to the moon or even another planet would provide a light condition of constant light. Currently, little is known regarding the effects of altered light/dark cycles on neurochemical levels within the central nervous system (CNS). Many biochemical, physiological and behavioral phenomena are under circadian control, governed primarily by the hypothalamic suprachiasmatic nucleus. As such, these phenomena are subject to influence by the environmental light/dark cycle. Circadian variations in locomotor and behavioral activities have been correlated to both the environmental light/dark cycle and to dopamine (DA) levels within the CNS. It has been postulated by Martin-Iverson et al. that DA's role in the control of motor activity is subject to modulation by circadian rhythms (CR), environmental lighting and excitatory amino acids (EAAs). In addition, DA and EAA receptor regulated pathways are involved in both the photic entrainment of CR and the control of motor activity. The cellular mechanisms by which DA and EAA-receptor ligands execute these functions, is still unclear. In order to help elucidate these mechanisms, we set out to determine the effects of altered environmental light/dark cycles on CNS neurotransmitter levels. In this study, we focused on the striatum, a region of the brain that receives a number of dopaminergic and glutamatergic input and is known to be involved in the modulation of locomotor and behavioral responses.

Sroufe, Angela E.↗

Light-Emitting Diodes (LED) for Primary Animal Habitat Lighting in Highly Controlled Environments

Significant alterations in Biological Clock responses have been reported following sidereal time changes (e.g., Jet-lag), and exposure to microgravity (e.g., daytime sleepiness). Additionally, light reduces circulating melatonin (spectral specificity greatest between 450-500 nm). It was hypothesized that LEDs can replace the current light sources used in zero gravity and terrestrial research laboratories because of their small size, low mass, low energy consumption and long functional life. This report evaluates the capacity of LEDs to entrain the circadian system of rats as judged by measurement of overt behavioral circadian rhythms (activity, feeding, drinking). These data were collected in highly controlled environments similar to the shuttle Animal Enclosure Modules. Two groups were compared: control - animals exposed to standard cool-white fluorescent lights, and test - animals exposed to LEDs with a spectral power distribution matching the fluorescent lights. Gross locomotor activity, feeding and drinking frequencies were continuously monitored and stored at 10 minute intervals. Animals were exposed to the following photoperiods: 28 days of 12L:12D, 19 days of 24L:0D and 16 days of 12L:12D. Light intensities tested varied between 0.1 to 100 lux. Rats received food and water ad libitum, and temperature and humidity were controlled throughout the study. The general health status of all rats was acceptable for each day of this study. No incidents of aggressive behavior were observed. Growth, locomotor activity, food and water consumption were comparable for all groups of animals, i.e, the circadian characteristics of the animals under these conditions were comparable. These results indicate that LED arrays are as effective in maintaining circadian rhythm stability as the commonly used cool-white fluorescent light sources. LEDs with their flexible spectrum, low energy requirements and minimal heat production have advantages for some chronopharmacology studies and for microgravity animal habitats.

Winget, C. M.↗

Alertness Management In Flight Operations: A NASA Education and Training Module

Since 1980, the NASA Ames Fatigue Countermeasures Program has been conducting research on sleep, circadian rhythms, and fatigue in a variety of flight operations 1. An original goal of the program was to return the scientific and operational knowledge to the aviation industry. To meet this goal, the NASA Ames Fatigue Countermeasures Program has created an Education and Training Module entitled, "Strategies for Alertness Management in Flight Operations." The Module was designed to meet three objectives: 1) explain the current state of knowledge about the physiological mechanisms underlying fatigue, 2) demonstrate how this knowledge can be applied to improve flight crew sleep, performance, and alertness, and 3) offer countermeasure recommendations. The Module is composed of two components: 1) a 60-minute live presentation provided by a knowledgeable individual and 2) a NASA/FAA Technical Memorandum (TM) that contains the presentation materials and appendices with complementary information. The TM is provided to all individuals attending the live presentation. The Module content is divided into three parts: 1) basic information on sleep, sleepiness, circadian rhythms, fatigue, and how flight operations affect these physiological factors, 2) common misconceptions about sleep, sleepiness, and fatigue, and 3) alertness management strategies. The Module is intended for pilots, management personnel, schedulers, flight attendants, and the many other individuals involved in the aviation system.

Rosekind, Mark R.↗

CHOICE - Directed Study: Consequences of longterm- Confinement and Hypobaric HypOxia on Immunity in the Antarctic Concordia Environment

Concerning ground-based space physiological research, the choice of analog must carefully match the system of interest. For spaceflight-associated immune dysregulation (SAID), Antarctica winter-over has emerged as potentially the best terrestrial analog. The prolonged mission durations, extreme/dangerous environment, station-based lifestyle, isolation from outside world, disrupted circadian rhythms, and other psychological aspects make this analog extremely high fidelity for exploration-class space missions (long duration lunar, Mars). NASA, ESA and RSA are currently investigating SAID, with NASA currently operating the Integrated Immune flight study. It is desirable to have a ground analog for SAID validated, so that potential countermeasures might be validated terrestrially prior to during flight. For this presentation, NASA data collected on the winterover 2009 crewmembers, baseline through early deployment will be presented. Through early deployment (approximately 2-3 weeks at Concordia), phenotypic alterations included increased levels of memory T cells, shifts among the CD8+ T cell compartment to a more mature phenotype, and increases in constitutively activated T cells. CD8+/IFNg+ T cell percentages, and T cell blastogenesis functional responses were depressed early deployment as compared to healthy controls. In four compatible subjects, secreted T cell Th1/Th2 cytokines were measured following culture stimulation, and a Th2 shift was observed as compared to controls. Post-winter over frozen sample return will be required to determine if this shift persisted during the winter over period. Additionally, circadian rhythms remained altered compared to baseline, as determined through 5x daily cortisol measurements. Latent viral reactivation will not be determined until frozen sample return occurs.

Sams, Clarence↗

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Crucian, B. E.↗

Subjective alertness rhythms in elderly people

The aim of this study was to evaluate age-related changes in the circadian rhythm of subjective alertness and to explore the circadian mechanisms underlying such changes. Using a visual analogue scale (VAS) instrument, 25 older men and women (71 y and older; 15 female, 10 male) rated their subjective alertness about 7 times per day during 5 baseline days of temporal isolation during which habitual bedtimes and waketimes were enforced. Comparisons were made with 13 middle-aged men (37-52 y) experiencing the same protocol. Advancing age (particularly in the men) resulted in less rhythmic alertness patterns, as indicated by lower amplitudes and less reliability of fitted 24-h sinusoids. This appeared in spite of the absence of any reliable age-related diminution in circadian temperature rhythm amplitude, thus suggesting the effect was not due to SCN weakness per se, but to weakened transduction of SCN output. In a further experiment, involving 36 h of constant wakeful bedrest, differences in the amplitude of the alertness rhythm were observed between 9 older men (79 y+), 7 older women (79 y+), and 17 young controls (9 males, 8 females, 19-28 y) suggesting that with advancing age (particularly in men) there is less rhythmic input into subjective alertness from the endogenous circadian pacemaker. These results may explain some of the nocturnal insomnia and daytime hypersomnia that afflict many elderly people.

NASA Discipline Regulatory Physiology↗

Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat

A subpopulation of neurons in the suprachiasmatic nucleus (SCN) is shown here to exhibit isoperiodic bursting activity. The period of discharge in these cells may be lengthened or the periodicity may be transiently disrupted by photic stimulation. It is suggested that many, if not all, of these cells are vasoactive intestinal polypeptide (VIP) neurons. It is shown that the ultradian periodicity of these cells, estimates of the VIP neuron population size in the SCN, effects of partial lesions on tau (period), and estimates of the phase stability of SCN-driven circadian rhythms are consistent with a strongly coupled, multioscillator model of circadian rhythmicity, in which the oscillator population constitutes a restricted subset of the SCN neuronal population.

NASA Discipline Regulatory Physiology↗

Endogenous thermoregulatory rhythms of squirrel monkeys in thermoneutrality and cold

Whole body heat production (HP) and heat loss (HL) were examined to determine if the free-running circadian rhythm in body temperature (Tb) results from coordinated changes in HP and HL rhythms in thermoneutrality (27 degrees C) as well as mild cold (17 degrees C). Squirrel monkey metabolism (n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of Tb and activity. Feeding was also measured. Rhythms of HP, HL, and conductance were tightly coupled with the circadian Tb rhythm at both ambient temperatures (TA). At 17 degrees C, increased HP compensated for higher HL at all phases of the Tb rhythm, resulting in only minor changes to Tb. Parallel compensatory changes of HP and HL were seen at all rhythm phases at both TA. Similar time courses of Tb, HP, and HL in their respective rhythms and the relative stability of Tb during both active and rest periods suggest action of the circadian timing system on Tb set point.

NASA Discipline Regulatory Physiology↗

Biochronometry; Proceedings of the Symposium, Friday Harbor, Wash., September 4-6, 1969.

Topics discussed include circadian activity rhythms in birds and man, variation of circadian rhythms in monkeys, resetting of circadian eclosion rhythm in fruitflies, the effectiveness of mathematical models of circadian rhythms, the influence of ac electric fields on circadian rhythms in man, the relation between changes in the metabolic rate and circadian periodicity of the resistance of pocket mice to ionizing radiation, the relation between circadian organization and the photoperiodic time measurement in moths, the circadian rhythm of optic nerve potentials in the isolated eye of the sea hare, phasing of circadian temperature rhythms in the pocket mouse by specific spectral regions, the phase-shifting effect of light on circadian rhymicity in the fruifly, hormonal control of circadian rhythms in the fruitfly, metabolically controlled temperature compensation in the circadian rhythm of algae, and circadian rhythms in the chloroplasts of algae. Individual items are abstracted in this issue.

Menaker, M.↗