Progress 10/01/01 to 09/30/07
Outputs
Daily (circadian) rhythms are ubiquitous in vertebrates and are generated by an internal biological clock. We have conducted studies on the circadian and reproductive systems of birds, using the Japanese quail as a model. These studies showed that the circadian system of quail is comprised of multiple clocks and multiple photic inputs. The photic inputs include the eyes, the pineal organ, and extraretinal photoreceptors located in the brain. The main circadian pacemaker is located in the eyes and the ocular pacemakers control subordinate clocks located in the hypothalamus. Evidence that the eyes contain a biological clock and that they play a major role within the circadian system include the observations that the eyes can show a daily rhythm of secretion of the hormone melatonin in organ culture and that removal of the eyes causes a major disruption of the circadian system. The ocular clocks control the hypothalamic clocks via both a neural output and via the rhythmic
synthesis and release of melatonin. The ocular clocks in the two eyes of quail are tightly coupled one to another; for example, these two clocks will rapidly regain their normal phase-relationship after being driven out of phase with each other. We have also demonstrated that reproductive steroid hormones play a significant role in the circadian system of quail. For example, daily administration of estradiol or testosterone can entrain the circadian clock. Furthermore, the oviposition (egg laying) pattern in Japanese quail is driven by a circadian clock and this clock is sensitive to the effects of ovarian hormones. Finally, we have conducted studies of the immune system of quail and have demonstrated an important role for the pineal organ and melatonin in both the cell mediated and humoral immune response. Pinealectomy results in depressed cellular and humoral immune responses and melatonin administration to pinealectomized birds will restore a normal immune response.
Impacts
The purpose of our research is to understand the mechanisms generating daily (circadian) rhythms in animals, using the Japanese quail as a model. Our research focused on identifying the location of biological clocks in vertebrates and understanding how these clocks are involved in important aspects of the animal's physiology, such as the immune response. Our recent findings support the hypothesis that the main biological clock in quail is located within the eyes and these ocular clocks control other subordinate clocks in the hypothalamus. Our findings that the hormone melatonin is importantly involved in mediating the immune response of quail could have practical applications; for example, melatonin administration (or its cheaper precursor tryptophan) could be used to enhance the immune response of poultry. In a more general context our studies have led to an increased understanding of the circadian system of animals and, insofar as the circadian system plays a major
role in animal health and well-being, our studies could lead to insights into the treatment of animal diseases. In humans, for example, manic-depressive illness, jet lag, seasonal depression, sleep disorders and immune disorders are all caused by disruptions of the circadian system.
Publications
- Steele, C. T., Tosini, G., Siopes, T., and Underwood, H. (2006) Time keeping by the quail's eye: Circadian regulation of melatonin production. General and Comparative Endocrinology 145: 232-236.
- Underwood, H. (2007)Circadian organization in non-mammalian vertebrates. In L. Squire, T. Albright, F. Bloom, F. Gage and N. Spitzer (eds.) The New Encyclopedia of Neuroscience. Elsevier LTD. Oxford, England (in press).
- Moore, C. B., Siopes, T. D., Steele, C. T., and Underwood, H. (2002) Pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain normal immune responses in Japanese quail (Coturnix coturnix japonica). General and Comparative Endocrinology, 126: 352-358.
- Steele, C. T., Zivkovic, B. D., Siopes, T., and Underwood, H. (2003) Ocular clocks are tightly coupled and act as pacemakers in the circadian system of Japanese quail. American Journal of Physiology Regul. Integr. Comp. Physiol. 284: R208-R218.
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Progress 10/01/05 to 09/30/06
Outputs
We have been studying the physiology and anatomy of the circadian system of vertebrates, using the Japanese quail as a model. These studies have identified several components of the circadian pacemaking system including the eyes and the suprachiasmatic area of the hypothalamus. The eyes are likely the master pacemaker in the system insofar as a clock in the eye controls the period and phase of other circadian clocks (located in the suprachiasmatic area) via both neural and hormonal (melatonin) outputs. The daily rhythm of melatonin secretion from the eyes and the pineal plays a major role in the quail's circadian system; melatonin is not stored in the eyes or pineal but is rapidly secreted into the blood with higher levels of melatonin being secreted at night. More recently we have been using our knowledge of the quail's circadian system to probe the role of the circadian system in the immune response of Japanese quail. A cutaneous basophil hypersensitivity reaction
to phytohemagglutinin is being used to measure the cellular immune response and a primary antibody response to a Chukar red blood cell suspension is being used to measure the humoral immune response. We have demonstrated that winter-like short daylengths enhance both the cellular and humoral immune response. Significantly, more melatonin is secreted at night by both the eyes and pineal organ under short-photoperiod light-dark cycles and melatonin is immuno-enhancing in quail supporting the hypothesis that the effects of daylength on the immune response are mediated via melatonin. Pineal melatonin secretion, however, may be more important than ocular melatonin secretion in mediating the immune response to photoperiod because pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain normal immune responses. Removal of the pineal gland, but not the eyes, reduces cellular and humoral immune responses. We have demonstrated that a strong diurnal cycle is
present in the immune response of Japanese quail and that this diurnal cycle is likely driven by the diurnal cycle in blood melatonin levels.
Impacts
The purpose of our research is to understand the mechanisms generating daily (circadian) rhythms in animals, using the Japanese quail as a model and to understand how biological clocks affect an animal's behavior and physiology. Circadian rhythms play a major role in animal health and well-being. In humans, for example, manic-depressive illness, jet lag, seasonal depression, sleep disorders and immune disorders are all caused by disruptions of the circadian system. Also, the effectiveness of drugs is greater when administered at one time of day than another. Our research focuses on identifying the location of biological clocks in vertebrates and understanding how these clocks control important aspects of the animal's physiology, such as the immune response. Our recent findings support the hypothesis that the main biological clock in quail is located within the eyes and this circadian pacemaker drives other circadian clocks located within the suprachiasmatic area of
the hypothalamus. The immune response of quail shows a robust daily rhythm in both the cellular and humoral immune response and this daily rhythm in immunity is likely due to the daily rhythm in blood levels of the hormone melatonin. These studies have yielded insights not only into the location of major components of the circadian system of vertebrates, but have also shown how these biological clocks are influencing the immune response.
Publications
- No publications reported this period
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Progress 10/01/04 to 09/30/05
Outputs
We have been investigating components of the circadian system of vertebrates using the Japanese quail as a model. Our studies supported the hypothesis that the major circadian pacemaker driving activity and body temperature rhythms is located within the eye. This ocular pacemaker drives another pacemaker located within the suprachiasmatic area of the hypothalamus via both neural and hormonal (melatonin) outputs. Furthermore the suprachiasmatic pacemakers may be sensitive to the feedback effects of gonadal steroids. Within the last year we focused our attention on two aspects of the quail's circadian system. First, the hypothesis that the eyes act as pacemakers was strengthened by demonstrating that (a) cultured retinal tissue could exhibit a rhythm of melatonin release, (b) the rhythm of melatonin release is directly entrainable by 24-h light-dark cycles, and (c) supplementation of the culture medium with serotonin is necessary for robust, rhythmic production of
melatonin in constant darkness. Second, we have examined further the hypothesis that steroid hormones may play an important role within the quail's circadian system and that embryonic exposure to maternal steroids may affect fundamental properties of the circadian clock. Gonadal steroids, such as testosterone, are differentially deposited in the egg by the mother and eggs laid later in the clutch have higher levels of hormone. We have recently demonstrated that fundamental circadian properties of the offspring, such as the period of the circadian clock, differ between birds that hatch from early versus late laid eggs. We propose that maternal steroids are having a major organizational effect on the circadian system of the offspring.
Impacts
The purpose of our research is to understand the mechanisms generating daily (circadian) rhythms in animals, using the Japanese quail as a model. Circadian rhythms play a major role in animal health and well-being. In humans, for example, manic-depressive illness, jet lag, seasonal depression, and sleep disorders are all caused by disruptions of the circadian system. Also, the effectiveness of drugs is greater when administered at one time of day than another. Our research focuses on identifying the location of biological clocks in vertebrates and understanding how these clocks are influenced by both internal (e.g., hormonal) and external (e.g., environmental cycles) factors. Our recent findings support the hypothesis that the main biological clock in quail is located within the eyes and this "circadian pacemaker" drives other circadian clocks located within the suprachiasmatic area of the hypothalamus. Furthermore, embryonic exposure to steroids deposited in the egg
by the hen may permanently alter the circadian properties of the adult quail. Prenatal exposure to differential levels of maternal hormones may explain why circadian properties, such as the period of the clock, show variation among adults in other vertebrates as well.
Publications
- Steele, C. T., Tosini, G., Siopes, T. and Underwood, H. 2005. Time keeping by the quail's eye: Circadian regulation of melatonin production. Gen. Comp. Endocrinol. http://www.sciencedirect.com
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Progress 10/01/03 to 09/30/04
Outputs
It has been shown in many different vertebrates that fundamental circadian properties, such as the endogenous period of the circadian clock, vary between individual of a species. However, surprisingly little is know about the origins of such variation. We have been investigating the physiology of circadian rhythms in homeotherms, using the Japanese quail as a model. Japanese quail lay eggs in clutches. We have recently shown significant differences in the circadian systems of birds hatched from eggs laid early in a clutch versus birds that hatch later in the clutch. For example, single injections of testosterone or estradiol will cause significant phase-shifts in the circadian rhythm of body temperature in adult birds hatched from late-clutch eggs while they have little effect in birds hatched from early-clutch eggs. Also, the endogenous circadian periods of birds hatched from late-clutch eggs are significantly longer than the periods shown by birds hatched from
early-clutch eggs. Hens deposit significant amounts of reproductive steroid hormones (testosterone, estradiol and progesterone) in the egg. Furthermore, a perusal of the literature shows that the levels of certain reproductive hormones in the eggs, such as testosterone, vary depending on when the egg is laid in the clutch; for example, greater amounts of testosterone are deposited in the eggs laid later in the sequence. We hypothesize, therefore, that exposure to differential levels of steroid hormones, such as testosterone, has an organizational effect on the circadian system of Japanese quail. This would be quite significant as, to our knowledge, there are no published studies on the organizational effects of prenatal exposure hormones on the circadian system of any vertebrate. The organizational effects of exposure to hormones could account for the variations in circadian properties of vertebrates and such variations may have significant adaptive value. We are currently
investigating if injections of reproductive steroids into the egg can lead to differences in the circadian properties of the adult quail.
Impacts
The purpose of our research is to understand the mechanisms generating daily (circadian) and seasonal rhythms in animals, using the Japanese quail as a model. All animals show a host of rhythms from the molecular level to the level of the whole organism. These rhythms play a major role in animal health and well-being. In humans, for example, manic-depressive illness, jet lag, seasonal depression, and sleep disorders are all caused by disruptions of the circadian system. Furthermore, the effectiveness of drugs, or the harmful effects of toxins, are greater at one time of day than another. Our research focuses on discovering the sites of the internal biological clocks and understanding how these clocks are influenced by both internal (e.g., hormonal) and external (e.g., environmental cycles) factors. Our recent findings support the hypothesis that embryonic exposure to reproductive steroids may permanently alter the circadian properties of the adult quail. This
mechanism may well explain the variation in circadian properties observed in adults of most vertebrates. Such variation may have significant adaptive value; for example, it could provide the basis for individual variations in the phase of various internal rhythms and daily environmental cycles. This could aid species survival as the circadian systems of some individuals could provide a match to variations in environmental cycles.
Publications
- No publications reported this period
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Progress 10/01/02 to 09/30/03
Outputs
Recently, an association between photoperiod (daylength) and various immune responses has been observed in both birds and mammals. Using the Japanese quail as a model we have shown that both the cellular and humoral components of the immune system are enhanced in short photoperiods as compared to long photoperiods. This response has survival value insofar as birds need an enhanced immune response to combat the stressful conditions of winter. We have shown that daylength controls the amount of the hormone melatonin produced by the pineal organ and the eyes: melatonin levels are high at night and low during the day so more melatonin is produced on shorter (winter) daylengths. To date, our studies support the hypothesis that melatonin mediates the effects of daylength on the immune system. Currently, we are investigating the daily (circadian) nature of both the cellular and humoral immune responses. The cellular response was assessed by measuring a cutaneous basophil
hypersensitivity reaction to a phytohemagglutinin antigen while primary antibody titers following injection of a Chukar red blood cell suspension were used to determine the humoral response. Antigens that invoke either the cellular or humoral immune response were injected at different times of day in quail entrained to a 24 hour light-dark cycle. A significant daily variation was observed in both the cellular and humoral immune response: the cellular response was more vigorous in response to antigen administered during the day while the humoral response was more vigorous to antigen administered during the night. These daily rhythms in immune response may be mediated by melatonin because birds lacking an endogenous rhythm of melatonin did not show the daily rhythms in immune response while birds administered melatonin for 12 hours per day showed daily rhythms in sensitivity to the antigens.
Impacts
These studies reveal the role of external factors, such as photoperiod, and the role of internal factors, such as the hormone melatonin, in the control of the immune response of Japanese quail. These findings can lead to ways to enhance the immune response of economically important avian species.
Publications
- Steele, C. T., Zivkovic, B. D., Siopes, T. and Underwood, H. 2003. Ocular clocks are tightly coupled and act as pacemakers in the circadian system of Japanese quail. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284: R208-R218.
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Progress 10/01/01 to 09/30/02
Outputs
Daily (circadian) rhythms are ubiquitous in vertebrates and are generated by an internal "biological clock". Using the Japanese quail as our model, we have shown that the eyes are the sites of major circadian pacemakers and, furthermore, the eyes communicate with clocks located in the hypothalamus via the cyclic synthesis and release of the hormone, melatonin. In addition, the pineal organ of quail also synthesizes and releases melatonin daily. Under light-dark cycles, the pineal contributes two-thirds of the melatonin to the blood and the eyes contribute the remaining one-third. We have recently assessed the role of melatonin in the immune response of Japanese quail. Pinealectomy, but not eye removal, significantly reduced the cellular and humoral responses of quail. Furthermore, melatonin administration to pinealectomized birds increased both the cellular and humoral immune responses to the level of control birds. These results show that melatonin is importantly
involved in the immune response of birds. Furthermore, the data show an important role of the pineal in the immune response: immunodepression is observed in birds in which two-thirds of the plasma removed by pinealectomy. Although the eyes secrete significant amounts of melatonin, eye removal alone is not sufficient to reduce cellular and humoral responses in Japanese quail.
Impacts
(N/A)
Publications
- Moore, C. B., Siopes, T. D., Steele, C. T. and Underwood, H. 2002. Pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain immune responses in Japanese quail (Coturnix coturnix japonica). Gen. Comp. Endocrinol. 126: 352-358.
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Progress 10/01/00 to 09/30/01
Outputs
na
Impacts
(N/A)
Publications
- No publications reported this period
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