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    Home > Active Ingredient News > Study of Nervous System > Nat Commun: Adenosine integrates light and sleep signals to regulate the circadian rhythm in mice

    Nat Commun: Adenosine integrates light and sleep signals to regulate the circadian rhythm in mice

    • Last Update: 2021-06-08
    • Source: Internet
    • Author: User
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    News from April 13, 2021 //---The accumulation of adenosine is closely related to the need for sleep, and the intake of caffeine can combat the stress of sleepiness.
    In addition, caffeine also directly affects the timing system of the biological clock, which has nothing to do with the physiological mechanism of sleep.
    However, we still don't know how caffeine affects the biological clock.
    In a recent study, the team of Sridhar R.
    Vasudevan from the University of Oxford in the United Kingdom identified an adenosine-based regulation mechanism that can interact with sleep and circadian processes to optimize sleep/waking time in mice.
    Related results were published in the recent "Nature Communications" magazine.




    (Image source:mammals, the suprachiasmatic nucleus (SCN) is considered the "biological clock pacemaker.
    " SCN is composed of multiple coupled neurons, and each neuron contains a molecular mechanism that produces circadian rhythm oscillations.
    The "molecular clockwork" in SCN accurately responds to changes in the time of the day by detecting changes in the quantity and quality of dawn and dusk through a special photoreceptor in the eye.


    Light causes the up-regulation of two key clock genes Per1 and Per2, and their expression determines the phase of the molecular clock.
    In turn, SCN coordinates the timing capabilities of the "peripheral biological clock" distributed in various organs of the human body.
    It is worth emphasizing that the "peripheral biological clock" may be affected by a variety of biological signals, including temperature, metabolites and hormones (such as glucocorticoids).
    The difference is that SCN is mainly affected by light.
    For example, although there is evidence that non-light stimuli including exercise can also have a significant effect on SCN, SCN has basically no response to glucocorticoids.
    In addition, because SCN is sensitive to caffeine, it indicates that there is a regulatory pathway based on endogenous adenosine, which is of great significance to the timing of circadian rhythms.


    Caffeine is the world's most popular stimulant and the most popular psychotropic drug.
    Caffeine has a variety of biological targets, but its anti-sleep stress effect is mediated through its antagonism to adenosine receptors.
    In addition to affecting sleep, several recent studies have shown that caffeine can also affect the circadian rhythm system, and this ability is independent of its sleep regulation ability.
    For example, studies have shown that 1) caffeine changes the expression of related genes in peripheral clock cells in vitro; 2) changes the movement rhythm of mice; 3) changes the frequency of action potentials in SCN in vivo and in vitro.
    In addition, caffeine can enhance the response of humans and other species to light.

    (Figure 1, the molecular mechanism of adenosine regulating the biological clock)

    It is still unclear how caffeine regulates the biological clock.
    In view of its involvement in the signal transduction pathway of adenosine, which has an important impact on sleep/wake behavior, the author believes that caffeine's regulation of the biological clock is also achieved through adenosine transduction.

    (Figure 1, SCN expresses adenosine receptors and can respond to adenosine antagonists)

    In this study, the author described the signaling pathway downstream of adenosine receptors that directly regulate the effects of the biological clock, and identified adenosine A1/A2A receptor antagonists specifically targeting this pathway.
    On this basis, the author found through in vivo and in vitro experiments that caffeine and adenosine changed the expression of clock genes and the circadian rhythm through the Ca2 + -ERK-AP-1 pathway.
    The results of animal physiology studies have shown that adenosine signaling regulates the response of mice to light by regulating sleep/wakeness.
    The effects of clinically tested adenosine receptor antagonists on mice at specific times can change their circadian rhythms.


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z

    In mammals, the suprachiasmatic nucleus (SCN) is considered the "biological clock pacemaker.
    " SCN is composed of multiple coupled neurons, and each neuron contains a molecular mechanism that produces circadian rhythm oscillations.
    The "molecular clockwork" in SCN accurately responds to changes in the time of the day by detecting changes in the quantity and quality of dawn and dusk through a special photoreceptor in the eye.


    Light causes the up-regulation of two key clock genes Per1 and Per2, and their expression determines the phase of the molecular clock.
    In turn, SCN coordinates the timing capabilities of the "peripheral biological clock" distributed in various organs of the human body.
    It is worth emphasizing that the "peripheral biological clock" may be affected by a variety of biological signals, including temperature, metabolites and hormones (such as glucocorticoids).
    The difference is that SCN is mainly affected by light.
    For example, although there is evidence that non-light stimuli including exercise can also have a significant effect on SCN, SCN has basically no response to glucocorticoids.
    In addition, because SCN is sensitive to caffeine, it indicates that there is a regulatory pathway based on endogenous adenosine, which is of great significance to the timing of circadian rhythms.


    Caffeine is the world's most popular stimulant and the most popular psychotropic drug.
    Caffeine has a variety of biological targets, but its anti-sleep stress effect is mediated through its antagonism to adenosine receptors.
    In addition to affecting sleep, several recent studies have shown that caffeine can also affect the circadian rhythm system, and this ability is independent of its sleep regulation ability.
    For example, studies have shown that 1) caffeine changes the expression of related genes in peripheral clock cells in vitro; 2) changes the movement rhythm of mice; 3) changes the frequency of action potentials in SCN in vivo and in vitro.
    In addition, caffeine can enhance the response of humans and other species to light.

    (Figure 1, the molecular mechanism of adenosine regulating the biological clock)

    It is still unclear how caffeine regulates the biological clock.
    In view of its involvement in the signal transduction pathway of adenosine, which has an important impact on sleep/wake behavior, the author believes that caffeine's regulation of the biological clock is also achieved through adenosine transduction.

    (Figure 1, SCN expresses adenosine receptors and can respond to adenosine antagonists)

    In this study, the author described the signaling pathway downstream of adenosine receptors that directly regulate the effects of the biological clock, and identified adenosine A1/A2A receptor antagonists specifically targeting this pathway.
    On this basis, the author found through in vivo and in vitro experiments that caffeine and adenosine changed the expression of clock genes and the circadian rhythm through the Ca2 + -ERK-AP-1 pathway.
    The results of animal physiology studies have shown that adenosine signaling regulates the response of mice to light by regulating sleep/wakeness.
    The effects of clinically tested adenosine receptor antagonists on mice at specific times can change their circadian rhythms.


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z


    Light causes the up-regulation of two key clock genes Per1 and Per2, and their expression determines the phase of the molecular clock.
    In turn, SCN coordinates the timing capabilities of the "peripheral biological clock" distributed in various organs of the human body.
    It is worth emphasizing that the "peripheral biological clock" may be affected by a variety of biological signals, including temperature, metabolites and hormones (such as glucocorticoids).
    The difference is that SCN is mainly affected by light.
    For example, although there is evidence that non-light stimuli including exercise can also have a significant effect on SCN, SCN has basically no response to glucocorticoids.
    In addition, because SCN is sensitive to caffeine, it indicates that there is a regulatory pathway based on endogenous adenosine, which is of great significance to the timing of circadian rhythms.


    Caffeine is the world's most popular stimulant and the most popular psychotropic drug.
    Caffeine has a variety of biological targets, but its anti-sleep stress effect is mediated through its antagonism to adenosine receptors.
    In addition to affecting sleep, several recent studies have shown that caffeine can also affect the circadian rhythm system, and this ability is independent of its sleep regulation ability.
    For example, studies have shown that 1) caffeine changes the expression of related genes in peripheral clock cells in vitro; 2) changes the movement rhythm of mice; 3) changes the frequency of action potentials in SCN in vivo and in vitro.
    In addition, caffeine can enhance the response of humans and other species to light.

    (Figure 1, the molecular mechanism of adenosine regulating the biological clock)

    It is still unclear how caffeine regulates the biological clock.
    In view of its involvement in the signal transduction pathway of adenosine, which has an important impact on sleep/wake behavior, the author believes that caffeine's regulation of the biological clock is also achieved through adenosine transduction.

    (Figure 1, SCN expresses adenosine receptors and can respond to adenosine antagonists)

    In this study, the author described the signaling pathway downstream of adenosine receptors that directly regulate the effects of the biological clock, and identified adenosine A1/A2A receptor antagonists specifically targeting this pathway.
    On this basis, the author found through in vivo and in vitro experiments that caffeine and adenosine changed the expression of clock genes and the circadian rhythm through the Ca2 + -ERK-AP-1 pathway.
    The results of animal physiology studies have shown that adenosine signaling regulates the response of mice to light by regulating sleep/wakeness.
    The effects of clinically tested adenosine receptor antagonists on mice at specific times can change their circadian rhythms.


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z


    Caffeine is the world's most popular stimulant and the most popular psychotropic drug.
    Caffeine has a variety of biological targets, but its anti-sleep stress effect is mediated through its antagonism to adenosine receptors.
    In addition to affecting sleep, several recent studies have shown that caffeine can also affect the circadian rhythm system, and this ability is independent of its sleep regulation ability.
    For example, studies have shown that 1) caffeine changes the expression of related genes in peripheral clock cells in vitro; 2) changes the movement rhythm of mice; 3) changes the frequency of action potentials in SCN in vivo and in vitro.
    In addition, caffeine can enhance the response of humans and other species to light.


    (Figure 1, the molecular mechanism of adenosine regulating the biological clock)

    It is still unclear how caffeine regulates the biological clock.
    In view of its involvement in the signal transduction pathway of adenosine, which has an important impact on sleep/wake behavior, the author believes that caffeine's regulation of the biological clock is also achieved through adenosine transduction.

    (Figure 1, SCN expresses adenosine receptors and can respond to adenosine antagonists)

    In this study, the author described the signaling pathway downstream of adenosine receptors that directly regulate the effects of the biological clock, and identified adenosine A1/A2A receptor antagonists specifically targeting this pathway.
    On this basis, the author found through in vivo and in vitro experiments that caffeine and adenosine changed the expression of clock genes and the circadian rhythm through the Ca2 + -ERK-AP-1 pathway.
    The results of animal physiology studies have shown that adenosine signaling regulates the response of mice to light by regulating sleep/wakeness.
    The effects of clinically tested adenosine receptor antagonists on mice at specific times can change their circadian rhythms.


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z
    (Figure 1, the molecular mechanism of adenosine regulating the biological clock)

    It is still unclear how caffeine regulates the biological clock.
    In view of its involvement in the signal transduction pathway of adenosine, which has an important impact on sleep/wake behavior, the author believes that caffeine's regulation of the biological clock is also achieved through adenosine transduction.


    (Figure 1, SCN expresses adenosine receptors and can respond to adenosine antagonists)

    In this study, the author described the signaling pathway downstream of adenosine receptors that directly regulate the effects of the biological clock, and identified adenosine A1/A2A receptor antagonists specifically targeting this pathway.
    On this basis, the author found through in vivo and in vitro experiments that caffeine and adenosine changed the expression of clock genes and the circadian rhythm through the Ca2 + -ERK-AP-1 pathway.
    The results of animal physiology studies have shown that adenosine signaling regulates the response of mice to light by regulating sleep/wakeness.
    The effects of clinically tested adenosine receptor antagonists on mice at specific times can change their circadian rhythms.


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z
    (Figure 1, SCN expresses adenosine receptors and can respond to adenosine antagonists)

    In this study, the author described the signaling pathway downstream of adenosine receptors that directly regulate the effects of the biological clock, and identified adenosine A1/A2A receptor antagonists specifically targeting this pathway.
    On this basis, the author found through in vivo and in vitro experiments that caffeine and adenosine changed the expression of clock genes and the circadian rhythm through the Ca2 + -ERK-AP-1 pathway.
    The results of animal physiology studies have shown that adenosine signaling regulates the response of mice to light by regulating sleep/wakeness.
    The effects of clinically tested adenosine receptor antagonists on mice at specific times can change their circadian rhythms.


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z


    In summary, the author has shown through a series of pharmacological and genetic methods that adenosine signals the circadian rhythm through Ca2 + -ERK-AP-1 and CREB/CRTC1-CRE pathways, as well as adenosine A1/A2A receptor signals.
    The clock genes Per1 and Per2 played a regulatory role.
    Studies have shown that these signal pathways converge and inhibit the same signal pathways activated by light.
    Therefore, the circadian rhythm of light can be systematically adjusted through the sleep history of animals.
    These findings help to understand how adenosine integrates signals from light and sleep, thereby regulating the circadian rhythm of mice, and provides a powerful therapeutic target for the stabilization of circadian rhythm disorders.
    (Bioon.
    com)

    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z


    Original source: Jagannath, A.
    , Varga, N.
    , Dallmann, R.
    et al.
    Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun 12, 2113 (2021).
    https://doi.
    org/10.
    1038/s41467-021-22179-z
    Original source: Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
    Nat Commun
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