Progress 01/01/12 to 12/31/12
Outputs
OUTPUTS: The circadian timing system is responsible for the internal and external temporal coordination of an organism over the course of a 24-h day. Casein kinase (CK)-mediated protein phosphorylation regulates circadian timing in the site of the master clock, the suprachiasmatic nuclei of the hypothalamus. During this period, we examined and reported on the effects of casein kinase 1 family inhibition on the regulation of circadian rhythm timing and sleep homeostasis in the non-human primate. The results of this work were reported to the relevant community of interest at the annual meeting of the Associated Professional Sleep Societies. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: We are working to provide data for future applications involving light for circadian and sleep disorders in medicine, as well as design criteria for utilizing light for optimum health and performance of various populations, including the agricultural industry. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We are continuing our circadian and polysomnographic (sleep) analyses of the responses to light of selective spectral content presented at different times of day as part of the development of our understanding the basis for potential light applications to improve health. The manipulation of CK mediated alterations of the clock represent: 1) a putative pathway for light effects on the circadian clock, and 2) an initial demonstration of timing effects of CK inhibition limited to circadian homeostasis, without alteration of another homeostatic system, i.e., sleep homeostasis. Past and pending publications will extend the knowledge base regarding the health effects of light. Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural products (animals and plants). The circadian system not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction and has an underlying influence on organism metabolism. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- Fuller, C. A., Robinson, E. L., Hoban-Higgins, T. M., Offord, J., DeMarco, G., Doran, A., Chandrasekaran, R., Wager, T., and Delnomdedieu, M. 2012. Effect of CK1 Inhibition on Rhesus Monkey Sleep Architecture and Circadian Rhythms. Sleep Abstract Supplement 35:A66.
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Progress 10/01/07 to 09/30/12
Outputs
Target Audience:We are working to provide data for future applications involving light for circadian and sleep disorders in medicine, as well as design criteria for utilizing light for optimum health and performance of various populations, including the agricultural industry. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
We are continuing our circadian and polysomnographic (sleep) analyses of the responses to light of selective spectral content presented at different times of day as part of the development of our understanding the basis for potential light applications to improve health. The manipulation of CK mediated alterations of the clock represent: 1) a putative pathway for light effects on the circadian clock, and 2) an initial demonstration of timing effects of CK inhibition limited to circadian homeostasis, without alteration of another homeostatic system, i.e., sleep homeostasis. Past and pending publications will extend the knowledge base regarding the health effects of light. Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural products (animals and plants). The circadian system not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction and has an underlying influence on organism metabolism. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
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Progress 01/01/11 to 12/31/11
Outputs
OUTPUTS: The circadian timing system is responsible for the internal and external temporal coordination of an organism over the course of a 24-h day. Casein kinase (CK)-mediated protein phosphorylation regulates circadian timing in the site of the master clock, the suprachiasmatic nuclei of the hypothalamus. During this period, we examined the effects of casein kinase 1 family inhibition on the regulation of circadian rhythm timing and sleep homeostasis in the non-human primate. The results of this work will be reported to the relevant community of interest at the annual meeting of the Associated Professional Sleep Societies. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: We are working to provide data for future applications involving light for circadian and sleep disorders in medicine, as well as design criteria for utilizing light for optimum health and performance of various populations PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We are continuing our circadian and polysomnographic (sleep) analyses of the responses to light of selective spectral content presented at different times of day as part of the development of our understanding the basis for potential light applications to improve health. The manipulation of CK mediated alterations of the clock represent: 1) a putative pathway for light effects on the circadian clock, and 2) an initial demonstration of timing effects of CK inhibition limited to circadian homeostasis, without alteration of another homeostatic system, i.e., sleep homeostasis. Past and pending publications will extend the knowledge base regarding the health effects of light. Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural products. The circadian system not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction and has an underlying influence on organism metabolism. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- No publications reported this period
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Progress 01/01/10 to 12/31/10
Outputs
OUTPUTS: We continue to collaborate with the California Lighting Technology Center (CLTC) on the health benefits of light. During this period the PI and CLTC met several times and reviewed issues and protocols for appropriate lighting for seniors living in residential facilities. The purpose of the meetings was to develop and disseminate information related to this topic to others working in this area. In particular, the PI also supported and continued to participate in meetings with Eskaton and Phillips Lighting. PARTICIPANTS: Dr. Charles A. Fuller, Professor of Neurobiology and Physiology directed this project. Drs. Edward L Robinson and Tana Hoban-Higgins provided scientific support and day-to-day management. Dr. Konstantinos Papamichael, Associate Director of California Lighting and Technology Center, UC Davis, provided liaison and technical expertise on existing and in-development lighting technologies and applications. TARGET AUDIENCES: We are endeavoring to provide basic findings for future applications involving light for circadian and sleep disorders in medicine, as well as design criteria for utilizing light for optimum health and performance of various populations. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We are continuing our polysomnographic analyses of the responses of sleep and circadian rhythms to light of selective spectral content presented at different times of day as part of the development of our understanding the basis for potential light applications to improve health. We continue to evaluate studies examining the response of the immune system, a key target to altered sleep schedules, as a model for sleep and circadian changes. Initial findings from our analysis suggest a complex role for light in gating sleep and wake onsets. Past and pending publications will extend the knowledge base regarding the health effects of light. Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural products. The CTS not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction and has an underlying influence on organism metabolism. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- No publications reported this period
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: We continue to collaborate with the California Lighting Technology Center (CLTC) on the health benefits of light. During this period the PI and CLTC met several times and reviewed issues and protocols for appropriate lighting for seniors living in residential facilities. The purpose of the meeting was to develop and disseminate information related to this topic to others working in this area. In particular, the Pi also supported and participated in a meeting with Eskaton and Phillips Lighting. PARTICIPANTS: Dr. Charles A. Fuller, Professor of Neurobiology and Physiology directed this project. Drs. Edward L Robinson and Tana Hoban-Higgins provided scientific support and day-to-day management. Dr. Konstantinos Papamichael, Associate Director of California Lighting and Technology Center, UC Davis, provided liaison and technical expertise on existing and in-development lighting technologies and applications. TARGET AUDIENCES: We are endeavoring to provide basic findings for future applications involving light for circadian and sleep disorders in medicine, as well as design criteria for utilizing light for optimum health and performance of various populations. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We are continuing our analysis of the response of sleep and circadian rhythms to light of selective spectral content presented at different times of day as an initial part of understanding the basis for potential light applications to improve health. We continue to evaluate studies examining the response of the immune system, a key target to altered sleep schedules, as a model for sleep and circadian changes. Initial findings from our analysis suggest a complex role for light in gating sleep and wake onsets. Past and pending publications will extend the knowledge base regarding the health effects of light. Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural products. The CTS not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- No publications reported this period
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: We continue to collaborate with the California Lighting Technology Center on the health benefits of light. During this period the PI co-organized a meeting on Light and Health with the California Light and Technology Center (CLTC). The purpose of the meeting was to disseminate information related to this topic to other California health professionals and scientists, utility organizations and design professionals. The Pi also supported and participated in a second symposia on Outdoor Lighting. PARTICIPANTS: Dr. Charles A. Fuller, Professor of Neurobiology and Physiology directed this project. Dr. Edward L Robinson provided scientific support and day-to-day management. Ms. Elizabeth Ingham provided technical and managerial support. Dr. Konstantinos Papamichael, Associate Director of California Lighting and Technology Center, UC Davis, provided liaison and technical expertise on existing and in-development lighting technologies and applications. TARGET AUDIENCES: We are endeavoring to provide basic findings for future applications involving light for circadian and sleep disorders in medicine, as well as design criteria for utilizing light for optimum health and performance of various populations. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We are currently performing analysis of the response of sleep and circadian rhythms to light of selective spectral content presented at different times of day as an initial part of understanding the basis for potential light applications to improve health. We continue to evaluate studies examining the response of the immune system, a key target to altered sleep schedules, as a model for sleep and circadian changes. Initial findings from our analysis suggest a complex role for light in gating sleep and wake onsets. A major finding is that while blue light can serve as an alerting stimulus, a reactive increase in sleep occurs following blue light exposure which appears to be independent of daily sleep drive and may act independently from the circadian rhythm of arousal and sleep timing. We have completed renovations to the primate centrifuge facility to improve our ability to study responses to light in altered acceleration environments. Past and pending publications will extend the knowledge base regarding the health effects of light. Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural products. The CTS not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- Hsieh, K.C., E.L. Robinson, and C.A. Fuller, Sleep architecture in unrestrained rhesus monkeys (Macaca mulatta) synchronized to 24-hour light-dark cycles. Sleep, 2008. 31(9): p. 1239-1250.
- Barger, L.K., T.M. Hoban-Higgins, and C.A. Fuller, Assessment of circadian rhythms throughout the menstrual cycle of female rhesus monkeys. American Journal of Primatology, 2008. 70(1): p. 19-25.
- Robinson, E.L., P. M. Fuller and C.A. Fuller, Blue light affects timing of sleep in rhesus monkeys but not sleep homeostasis. Presented at the ESRS meeting, Edinburgh, Scotland, 2008.
- Robinson, E.L. and C.A. Fuller, Blue light phase advances entrained rhythms of brain temperature and sleep in rhesus monkeys, FASEB J, 2008 22:1222.4, presented at EB 2008, San Diego, CA.
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Progress 01/01/07 to 12/31/07
Outputs
This research program continues to focus on the response of the circadian timing system (CTS) of primates to altered lighting conditions. We have completed studies of the response of the CTS to altered lighting schedules in male and female rhesus monkeys and have begun to characterize the response of the primate CTS to altered lighting spectra in male rhesus monkeys. The light-dark cycle has been shown to be the most effective time cue (or zeitgeber) for the mammalian circadian pacemaker. Our recent studies have confirmed that the spectral quality as well as timing of light exposure acts as an important circadian cue. We have shown that blue light, acting via novel photosensitive retinal ganglion cells, has complex effects on sleep and circadian rhythms. We have shown that in addition to promoting alertness in the evening, blue light paradoxically increases daytime sleep. Further, we have shown that blue light alters the timing of the circadian system relative to the
external day. These and other studies will aid in the design and implementation of light-dark and sleep-wake schedules that will best offset any physiological, behavioral or performance decrements resulting from compromised circadian function.
Impacts
Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural stock. The CTS not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- Ingham, E, Hoban-Higgins, T. M. Robinson, E. L. and Fuller, C. A. 2007. Sleep Disruption and Peripheral Blood Mononuclear Cell Cytokine Release in Rhesus Macaques. Society for Neuroscience (abstr.).
- Lu, J., Fuller, P. M., Hoban-Higgins, T. M., Fuller, C. A. and C. B. Saper 2007. Neurons of the rhesus macaque ventrolateral preoptic nucleus are sleep-active. Society for Neuroscience (abstr.).
- Robinson, E. L. and Fuller, C. A. 2007. Intermittent Blue Light Exposure Increases Daytime Sleep in Rhesus Monkeys. NASA HRP Investigators Workshop, Houston, TX January 2007.
- Robinson, E. L. Washburn D. A., and C. A. Fuller 2007. Blue Light Effects Depend on Time of Exposure in Rhesus Monkeys. Society for Neuroscience (abstr.).
- Barger, L. K., Hoban-Higgins, T. M. and C. A. Fuller 2007. Assessment of circadian rhythms throughout the menstrual cycle of female rhesus monkeys. Am. J. Primatol. 69:1-10.
- Hsieh, K.-C., E. L. Robinson and C. A. Fuller 2007. Sleep Architecture in unrestrained rhesus monkeys (Macaca mulatta) synchronized to 24-hour light-dark cycles. (submitted to Sleep).
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Progress 01/01/06 to 12/31/06
Outputs
This research program continues to focus on the response of the circadian timing system (CTS) of primates to altered lighting conditions. We have completed studies of the response of the CTS to altered lighting schedules in male and female rhesus monkeys and have begun to characterize the response of the primate CTS to altered lighting spectra in male rhesus monkeys. The light-dark cycle has been shown to be the most effective time cue (or zeitgeber) for the mammalian circadian pacemaker. Our studies have confirmed that the timing as well as the intensity of the light environment serve as important circadian cues. A novel melanopsin-containing photoreceptor that appears to send input to the circadian pacemaker has recently been identified. We have on-going studies that suggest that light in the blue part of the spectrum is more efficacious in influencing the primate CTS than is white light. These and other studies will aid in the design and implementation of
light-dark and sleep-wake schedules that will best offset any physiological, behavioral or performance decrements resulting from compromised circadian function.
Impacts
Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normal physiology and behavior, both in humans and in agricultural stock. The CTS not only regulates the timing of daily events, but also controls annual cycles, such as seasonal reproduction. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- Robinson, E. L., Hsieh, K.-C., Hoban-Higgins, T. M., Fuller C. A. 2006. Gender differences in sleep of unrestrained rhesus monkeys. Neuroscience (abstr) online.
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Progress 01/01/05 to 12/31/05
Outputs
This research program has made significant progress in elucidating the mechanisms underlying the response of the circadian timing system (CTS) of primates to altered lighting conditions. We have completed studies of the response of the CTS to altered lighting in both female and male rhesus monkeys. The lighting environment can have a direct effect on a rhythm separate from light's ability to synchronize the biological clock. These effects are referred to as masking. We utilized high frequency light-dark cycles to determine the direct effect of the ambient lighting environment on the circadian sleep-wake rhythm in rhesus monkeys. This study assessed the effect of a 2-hour period of light or darkness at each time of day. Over the 24-hour day, the presence of light stimulated wake while the presence of darkness induced sleep. During the light periods, animals spent approximately 75% of time awake and 25% of time asleep. This ratio was reversed during the dark periods.
The underlying circadian rhythm in sleep and wakefulness was preserved, and the masking effects of light and darkness superimposed upon it. Understanding the response of the CTS, and especially the sleep-wake rhythm, to altered lighting environments is critical for our understanding of how best to preserve human health while living and working in a society that functions 24-hours a day. These and other studies will aid in the design and implementation of light-dark and sleep-wake schedules that will best offset any physiological, behavioral or performance decrements resulting from compromised circadian function.
Impacts
Our studies relate directly to human welfare and agricultural production. Proper circadian function is crucial for maintaining normative physiology and behavior, both in humans and in agricultural stock. Understanding the regulatory mechanisms that control and coordinate circadian rhythms will allow development of techniques and treatments that will promote human health and optimize the growth, reproduction and health of agricultural stock.
Publications
- No publications reported this period
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Progress 01/01/04 to 12/31/04
Outputs
This research program has made significant progress in examination of the mechanisms underlying the response of the circadian timing system (CTS) of primates to altered force environments. We have completed studies of the response of the CTS to hypergravity in female and male rhesus monkeys. Our primary finding was a reduction in the sensitivity of the CTS to light. This resulted in a diminished capacity to entrain to ambient light-dark cycles and altered masking, e.g. increased body temperature, as a result of light exposure. The CTS period did not significantly differ in hypergravity and CTS output, e.g. the endogenous body temperature rhythm, showed acclimation to hypergravity. We also completed studies comparing entrainment to a 24-h solar and 24.67-h martian daylength in male and female rhesus monkeys. Entrainment to the longer martian day was seen when light intensity was adequate for entrainment, around 80 lux or equivalent. In dim light (< 10 lux) poor
entrainment was seen, including a free-runnnig body temperature rhythm in one animal. Sleep changes in hypergravity and in the martian day are being evaluated. Understanding the response of the CTS to altered day length and altered gravity is crucial to extending the ability of humans to function in non-24-h environments, including isolated terrestrial environments (polar, submarines) as well as in shift work. These and subsequent studies will help insure satisfactory health and performance for environments with altered physical loading and light-dark schedules.
Impacts
Our studies relate directly to human welfare and agricultural production. Circadian rhythms in human physiology and performance are critical to health. Identifying underlying regulatory mechanisms of the circadian clock, and their relationship to the environment could lead to treatments that promote health and well being. Similarly, the circadian system is critical to agricultural stock growth, reproduction and health. Understanding the role of the environment in this system can have a direct benefit to agriculture.
Publications
- Hsieh K.C., E.L. Robinson, and C.A. Fuller. Effects of short light-dark cycles on sleep in rhesus monkeys. (abstract submitted to 2005 APSS meeting).
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Progress 01/01/03 to 12/31/03
Outputs
This research program has made significant progress in examination of the mechanisms underlying the response of the circadian timing system (CTS) of primates to altered gravity and light. We have also instituted studies of sleep in a primate model for human sleep. The forced desynchrony protocol has been, for the first time, applied to determining how the CTS responds to altered gravity. Using chronic centrifugation at low G levels, we have compared the endogenous periodicity of the CTS at 2G with normal earth gravity. Results to date from male rhesus suggest that the period of the body's clock is shorter with increased G level. Further, the amplitude of the body temperature rhythm is depressed by increased G load. Sleep was also affected by increased G. Fragmentation of sleep was seen after acclimation to 2G. Increased deep (slow-wave) sleep was also seen. We also studied the response of the CTS to the longer day expected on Mars (24.67 h), using both solar and
simulated martian lighting. Both male and female rhesus were able to entrain to the longer day. Understanding the response of the CTS to altered day length is crucial to extending the ability of humans to function in non-24-h environments, including isolated terrestrial environments (polar, submarines) as well as in space. These and subsequent studies will help insure satisfactory health and performance for individuals working in environments with altered physical loading and light-dark schedules.
Impacts
Our studies relate directly to human welfare and agricultural production. Circadian rhythms in human physiology and performance are critical to health. Identifying underlying regulatory mechanisms of the circadian clock, and their relationship to the environment could lead to treatments that promote health and well being. Similarly, the circadian system is critical to agricultural stock growth, reproduction and health. Understanding the role of the environment in this system can have a direct benefit to agriculture.
Publications
- Hsieh, J. K, Robinson, E. L., and C. A. Fuller. Validation of an Automatic Sleep Scoring Program Using Neural Network. (abstract submitted to 2004 APSS meeting).
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Progress 01/01/02 to 12/31/02
Outputs
This research program has made significant progress in examination of the mechanisms underlying the response of the circadian timing system (CTS) of primates to altered gravity. We have also instituted studies of sleep in a primate model for human sleep. The forced desynchrony protocol has been, for the first time, applied to determining how the CTS responds to altered gravity. Using chronic centrifugation at low G levels, we have compared the endogenous periodicity of the CTS at two G levels with normal earth gravity. Preliminary analysis showed that the period of the body's clock is longer with increased G level. Further, the amplitude of the body temperature rhythm is depressed by increased G load. Sleep was also affected by increased G. Fragmentation of sleep was seen after acclimation to 2G. Increased deep (slow-wave) sleep was also seen. We have also initiated studies of the ability of the CTS to entrain to altered day length with both solar and simulated
martian lighting spectra. Determining how the CTS can adapt to altered day length will be crucial to extending the ability of humans to function in isolation from the normal 24-h day. This has implications for both isolated terrestrial environments (polar, submarine) and extra-terrestrial environments such as space craft and contained habitats. These and subsequent studies will contribute to known problems with sleep and circadian timing associated with space flight and provide a groundwork for maintenance of satisfactory health and performance for planetary exploration.
Impacts
Our studies relate directly to human welfare and agricultural production. Circadian rhythms in human physiology and performance are critical to health. Identifying underlying regulatory mechanisms of the circadian clock, and their relationship to the environment could lead to treatments that promote health and well being. Similarly, the circadian system is critical to agricultural stock growth, reproduction and health. Understanding the role of the environment in this system can have a direct benefit to agriculture.
Publications
- Robinson, E. L., Hsieh, J. K, and C. A. Fuller. A primate model of sleep regulation. . (submitted abstract APSS 2003 meeting).
- Robinson, E. L., Hoban-Higgins, T. M, J. K. Hsieh, and C. A. Fuller. Circadian period of rhesus monkeys in hypergravity. (submitted abstract FASEB 2003 meeting).
- Hsieh, J. K, Robinson, E. L., and C. A. Fuller. Response of unrestrained rhesus monkeys to 24-hour total sleep deprivation. (submitted abstract APSS 2003 meeting).
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Progress 01/01/01 to 12/31/01
Outputs
This research program has made significant progress in examination of the mechanisms underlying the regulation and control of the circadian timing system (CTS) of primates. We have studied a variety of rhythms in rhesus, both at 1 and 2G. In a 1G environment, the rhythm phases of body temperature, heart rate and activity were significantly delayed in females compared to males, although other rhythm properties were not different. In 2G, male rhesus responded with a decrease in mean body temperature, as seen in other mammals, however female mean body temperature increased. Both genders completed PTS performance tasks with a high degree of accuracy and speed at both 1G and 2G. We have also examined the ability of light and melatonin to phase shift female rhesus. Light pulses administered in the evening phase delayed body temperature rhythms, while melatonin phase advanced this rhythm. This pattern of phase shifting is the same as is seen in humans; thus these studies
have helped to establish the rhesus monkey as a model for human circadian rhythms. We have also used a forced desynchrony protocol to show that the circadian period of the rhesus monkey clock is close to that of humans. We have recently added the capability to measure sleep states in rhesus monkeys by means of telemetry and have completed several pilot studies. Sleep state organization in rhesus closely resembles that of humans. Hypergravity increased slow wave sleep and daytime naps, reduced REM sleep and altered the timing of sleep stages, principally by delaying deep SWS. We are currently studying the effects of hypergravity on the CTS, using forced desynchrony to clarify how the clock is affected by increased gravity. These and subsequent studies will address problems with sleep and circadian timing associated with spaceflight and planetary exploration.
Impacts
Our studies relate directly to human welfare and agricultural production. Circadian rhythms in human physiology and performance are critical to health. Identifying underlying regulatory mechanisms of the circadian clock, and their relationship to the environment could lead to treatments that promote health and well being. Similarly, the circadian system is critical to agricultural stock growth, reproduction and health. Understanding the role of the environment in this system can have a direct benefit to agriculture.
Publications
- Robinson, E. L., K-C. Hsieh, and C. A. Fuller. 2001. Circadian period of rhesus monkeys measured in a forced desynchrony protocol. FASEB Journal 15:A141.
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Progress 01/01/00 to 12/31/00
Outputs
This research program has made significant progress in its examination of the mechanisms underlying the regulation and control of the circadian timing system (CTS) of primates. We have studied rhythms in performance and other physiological variables in rhesus, both at 1 and 2G. In a 1G environment, there were no significant differences between genders in the daily means or amplitudes of the circadian rhythms of body temperature, heart rate, activity and drinking. However, rhythm phase was significantly delayed in females compared to males. The genders also differed in their response to a 2G environment. Our initial data analysis reveals that, while male rhesus respond to 2G with a decrease in mean body temperature (as has been seen in other mammals), females evidenced an increased mean body temperature as they adapted to the increased gravitational field. We then repeated our 1 and 2G studies with the females as subjects. As had been seen in the males, female rhesus
completed PTS tasks with a high degree of accuracy and speed at both 1G and 2G and also showed physiological alterations associated with the onset of 2G. We have also examined the ability of light and melatonin to phase shift female rhesus. Both one and two hour evening light pulses were shown to phase delay body temperature rhythms. Melatonin administered in the evening was shown to phase advance this rhythm. This pattern of phase shifting is the same as is seen in humans; thus these studies have helped to establish the rhesus monkey as a model for human circadian rhythms. We have recently used a forced desynchrony protocol, thought to be unsuitable for use with animals, to show that the circadian period of the rhesus monkey clock is close to that of humans. Additionally, during this period, we have added the capability to measure sleep states in rhesus monkeys by means of telemetry.
Impacts
Our studies relate directly to human welfare and agricultural production. Circadian rhythms in human physiology and performance are critical to health. Identifying underlying regulatory mechanisms of the circadian clock, and their relationship to the environment could lead to treatments that promote health and well being. Similarly, the circadian system is critical to agricultural stock growth, reproduction and health. Understanding the role of the environment in this system can have a direct benefit to agriculture.
Publications
- ROBINSON, E.L., HSIEH, K-C., HOBAN-HIGGINS, T.M. and FULLER, C.A. 2000. Evening bright light phase delays and evening melatonin phase advances circadian rhythms of rhesus monkeys. FASEB Journal 14:A451.2.
- ROBINSON, E.L. and FULLER, C.A. 2000. Gravity and thermoregulation: metabolic changes and circadian rhythms. Pflugers Arch. - Eur. J. Physiol., 441:R32-R38.
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Progress 01/01/99 to 12/31/99
Outputs
This research program has made significant progress in its examination of the mechanisms underlying the regulation and control of the circadian timing system (CTS) of primates. One of the goals of this research program is to elucidate any gender differences in the response of the circadian system. To achieve this objective, we had tracked the menstrual cyclicity of eight female rhesus for a year. Daily urine samples were collected and assayed for estrogen and progesterone conjugates. These data confirmed the cycling status of the females and the phase and onset of each individual animal's menstrual cycle. We have studied rhythms in performance and other physiological variables in rhesus, both at 1 and 2G. In a 1G environment, there were no significant differences between genders in the daily means or amplitudes of the circadian rhythms of body temperature, heart rate, activity and drinking. However, rhythm phase was significantly delayed in females compared to males.
The genders also differed in their response to a 2G environment. Our initial data analysis reveals that, while male rhesus respond to 2G with a decrease in mean body temperature (as has been seen in other mammals), females evidenced an increased mean body temperature as they adapted to the increased gravitational field. The 2G studies were performed on a 6 meter diameter centrifuge. Animals were housed in a module that allowed us to continuously record performance (via the Psychomotor Test System; PTS), body temperature, heart rate and drinking, and to collect urine. Physiological data were collected via telemetry, allowing us to study unrestrained animals; software was developed to allow for the circadian analysis of these data. We then repeated our 1 and 2G studies with the females as subjects. As had been seen in the males, female rhesus completed PTS tasks with a high degree of accuracy and speed at both 1G and 2G and also showed physiological alterations associated with the onset
of 2G. However, there were significant changes in circadian variables across the phases of the menstrual cycle. We will extend these studies to encompass other rhythms. We have also examined the ability of light and melatonin to phase shift female rhesus. Both one and two hour evening light pulses were shown to phase delay body temperature rhythms. Melatonin administered in the evening was shown to phase advance this rhythm. This pattern of phase shifting is the same as is seen in humans; thus these studies have helped to establish the rhesus monkey as a model for human circadian rhythms.
Impacts
Our studies relate directly to human welfare and agricultural production. Circadian rhythms in human physiology and performance are critical to health. Identifying underlying regulatory mechanisms of the circadian clock, and their relationship to the environment could lead to treatments that promote health and well being. Similarly, the circadian system is critical to agricultural stock growth, reproduction and health. Understanding the role of the environment in this system can have a direct benefit to agriculture.
Publications
- Robinson, E.L., Hsieh, K.-C.T., Hoban-Higgins, M. and Fuller, C.A. 2000. Evening bright light phase delays and evening melatonin phase advances circadian rhythms of rhesus monkeys. FASEB J. In press.
- Barger, L.K. and Fuller, C.A. 1999. Gender differences in the responses of rhesus monkeys to light phase shifts. FASEB J. 13(5):A739.
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