scholarly journals Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster

2009 ◽  
Vol 296 (2) ◽  
pp. R411-R418 ◽  
Author(s):  
Christina L. Ruby ◽  
Rebecca A. Prosser ◽  
Marc A. DePaul ◽  
Randy J. Roberts ◽  
J. David Glass
Keyword(s):  
Circadian Clock ◽  
Activity Rhythm ◽  
Direct Action ◽  
Glutamate Release ◽  
Extracellular Fluid ◽  
Circadian Rhythmicity ◽  
Phase Resetting ◽  
Circadian Phase ◽  
Acute Ethanol

Disrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT1A,7 agonist, 8-OH-DPAT. To explore the basis of these effects in the whole animal, we used microdialysis to characterize the pharmacokinetics of intraperitoneal injection of EtOH in the hamster SCN extracellular fluid compartment and then studied the effects of such EtOH treatment on photic and serotonergic phase resetting of the circadian locomotor activity rhythm. Peak EtOH levels (∼50 mM) from a 2 g/kg injection occurred within 20–40 min with a half-life of ∼3 h. EtOH treatment dose-dependently attenuated photic phase advances but had no effect on phase delays and, contrary to in vitro findings, markedly attenuated 8-OH-DPAT-induced phase advances. In a complementary experiment using reverse microdialysis to deliver a timed SCN perfusion of EtOH during a phase-advancing light pulse, the phase advances were blocked, similar to systemic EtOH treatment. These results are evidence that acute EtOH significantly affects photic and nonphotic phase-resetting responses critical to circadian clock regulation. Notably, EtOH inhibition of photic signaling is manifest through direct action in the SCN. Such actions could underlie the disruption of circadian rhythmicity associated with alcohol abuse.

Cocaine modulates pathways for photic and nonphotic entrainment of the mammalian SCN circadian clock

2012 ◽  
Vol 302 (6) ◽  
pp. R740-R750 ◽  
Author(s):  
J. David Glass ◽  
Allison J. Brager ◽  
Adam C. Stowie ◽  
Rebecca A. Prosser
Keyword(s):  
Circadian Clock ◽  
Receptor Antagonist ◽  
Serotonin Receptor ◽  
Activity Rhythm ◽  
Phase Shifts ◽  
Phase Delay ◽  
Phase Advance ◽  
Regulatory Pathways ◽  
Circadian Phase

Cocaine abuse is highly disruptive to circadian physiological and behavioral rhythms. The present study was undertaken to determine whether such effects are manifest through actions on critical photic and nonphotic regulatory pathways in the master circadian clock of the mouse suprachiasmatic nucleus (SCN). Impairment of SCN photic signaling by systemic (intraperitoneal) cocaine injection was evidenced by strong (60%) attenuation of light-induced phase-delay shifts of circadian locomotor activity during the early night. A nonphotic action of cocaine was apparent from its induction of 1-h circadian phase-advance shifts at midday. The serotonin receptor antagonist, metergoline, blocked shifting by 80%, implicating a serotonergic mechanism. Reverse microdialysis perfusion of the SCN with cocaine at midday induced 3.7 h phase-advance shifts. Control perfusions with lidocaine and artificial cerebrospinal fluid had little shifting effect. In complementary in vitro experiments, photic-like phase-delay shifts of the SCN circadian neuronal activity rhythm induced by glutamate application to the SCN were completely blocked by cocaine. Cocaine treatment of SCN slices alone at subjective midday, but not the subjective night, induced 3-h phase-advance shifts. Lidocaine had no shifting effect. Cocaine-induced phase shifts were completely blocked by metergoline, but not by the dopamine receptor antagonist, fluphenazine. Finally, pretreatment of SCN slices for 2 h with a low concentration of serotonin agonist (to block subsequent serotonergic phase resetting) abolished cocaine-induced phase shifts at subjective midday. These results reveal multiple effects of cocaine on adult circadian clock regulation that are registered within the SCN and involve enhanced serotonergic transmission.

Evolution Analysis of the Circadian Clock Protein KaiB

2013 ◽  
Vol 647 ◽  
pp. 391-395
Author(s):  
Liu Sen ◽  
Song Liu
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Feedback Loop ◽  
Circadian System ◽  
Circadian Rhythmicity ◽  
Physiological Functions ◽  
Clock System ◽  
Evolution Analysis ◽  
Clock Protein

Regulation of daily physiological functions with approximate a 24-hour periodicity, or circadian rhythms, is a characteristic of eukaryotes. So far, cyanobacteria are only known prokaryotes reported to possess circadian rhythmicity. The circadian system in cyanobacteria comprises both a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO can be reconstituted in vitro with three purified proteins (KaiA, KaiB, and KaiC) with the existence of ATP. Phase of the nanoclockwork has been associated with the phosphorylation states of KaiC, with KaiA promoting the phosphorylation of KaiC, and KaiB de-phosphorylating KaiC. Here we studied the evolution of the KaiB protein. The result will be helpful in understanding the evolution of the circadian clock system.

Involvement of glutamate release in substance P-induced phase delays of suprachiasmatic neuron activity rhythm in vitro

1999 ◽  
Vol 836 (1-2) ◽  
pp. 190-193 ◽  
Author(s):  
Toshiyuki Hamada ◽  
Shiro Yamanouchi ◽  
Akihito Watanabe ◽  
Shigenobu Shibata ◽  
Shigenori Watanabe
Keyword(s):  
Substance P ◽  
Activity Rhythm ◽  
Glutamate Release ◽  
Neuron Activity

scholarly journals A dual-feedback loop model of the mammalian circadian clock for multi-input control of circadian phase

2020 ◽  
Vol 16 (11) ◽  
pp. e1008459
Author(s):  
Lindsey S. Brown ◽  
Francis J. Doyle
Keyword(s):  
Circadian Clock ◽  
Small Molecules ◽  
Feedback Loop ◽  
Feedback Loops ◽  
The Body ◽  
Loop Model ◽  
Circadian Phase ◽  
Input Control ◽  
Cellular Components

The molecular circadian clock is driven by interlocked transcriptional-translational feedback loops, producing oscillations in the expressions of genes and proteins to coordinate the timing of biological processes throughout the body. Modeling this system gives insight into the underlying processes driving oscillations in an activator-repressor architecture and allows us to make predictions about how to manipulate these oscillations. The knockdown or upregulation of different cellular components using small molecules can disrupt these rhythms, causing a phase shift, and we aim to determine the dosing of such molecules with a model-based control strategy. Mathematical models allow us to predict the phase response of the circadian clock to these interventions and time them appropriately but only if the model has enough physiological detail to describe these responses while maintaining enough simplicity for online optimization. We build a control-relevant, physiologically-based model of the two main feedback loops of the mammalian molecular clock, which provides sufficient detail to consider multi-input control. Our model captures experimentally observed peak to trough ratios, relative abundances, and phase differences in the model species, and we independently validate this model by showing that the in silico model reproduces much of the behavior that is observed in vitro under genetic knockout conditions. Because our model produces valid phase responses, it can be used in a model predictive control algorithm to determine inputs to shift phase. Our model allows us to consider multi-input control through small molecules that act on both feedback loops, and we find that changes to the parameters of the negative feedback loop are much stronger inputs for shifting phase. The strongest inputs predicted by this model provide targets for new experimental small molecules and suggest that the function of the positive feedback loop is to stabilize the oscillations while linking the circadian system to other clock-controlled processes.

scholarly journals Acute Ethanol Disrupts Photic and Serotonergic Circadian Clock Phase-Resetting in the Mouse

2011 ◽  
pp. no-no ◽  
Author(s):  
Allison J. Brager ◽  
Christina L. Ruby ◽  
Rebecca A. Prosser ◽  
J. David Glass
Keyword(s):  
Circadian Clock ◽  
Phase Resetting ◽  
Acute Ethanol

HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway

2005 ◽  
Vol 289 (3) ◽  
pp. R656-R662 ◽  
Author(s):  
J. P. Clark ◽  
Christopher S. Sampair ◽  
Paulo Kofuji ◽  
Avindra Nath ◽  
Jian. M. Ding
Keyword(s):  
Nmda Receptor ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Glutamate Release ◽  
Phase Shifts ◽  
Channel Blockers ◽  
Light Entrainment ◽  
Transactivator Of Transcription

Patients infected with the human immunodeficiency virus (HIV), and other mammals infected with related lentiviruses, exhibit fatigue, altered sleep patterns, and abnormal circadian rhythms. A circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) temporally regulates these functions in mammals. We found that a secretary HIV transcription factor, transactivator of transcription (Tat), resets the murine circadian clock, in vitro and in vivo, at clinically relevant concentrations (EC50= 0.31 nM). This effect of Tat occurs only during the subjective night, when N-methyl-d-aspartate (NMDA) receptor [d-2-amino-5-phosphonovaleric acid (0.1 mM)] and nitric oxide synthase ( NG-nitro-l-arginine methyl ester, 0.1 mM) inhibitors block Tat-induced phase shifts. Whole cell recordings of SCN neurons within the brain slice revealed that Tat did not activate NMDA receptors directly but potentiated NMDA receptor currents through the enhancement of glutamate release. Consistent with this presynaptic mechanism, inhibitors of neurotransmission block Tat-induced phase shifts, such as tetrodotoxin (1 μM), tetanus toxin (1 μM), P/Q/N type-calcium channel blockers (1 μM ω-agatoxin IVA and 1 μM ω-conotoxin GIVA) and bafilomycin A1(1 μM). Thus the effect of Tat on the SCN may underlie lentiviral circadian rhythm dysfunction by operating as a disease-dependent modulator of light entrainment through the enhancement of excitatory neurotransmission.

scholarly journals Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro

Neuroscience ◽  
2008 ◽  
Vol 152 (3) ◽  
pp. 837-848 ◽  
Author(s):  
R.A. Prosser ◽  
C.A. Mangrum ◽  
J.D. Glass
Keyword(s):  
Circadian Clock ◽  
Phase Shifts ◽  
Acute Ethanol

Aging alters the phase-resetting properties of a serotonin agonist on hamster circadian rhythmicity

1995 ◽  
Vol 268 (1) ◽  
pp. R293-R298 ◽  
Author(s):  
P. D. Penev ◽  
P. C. Zee ◽  
E. P. Wallen ◽  
F. W. Turek
Keyword(s):  
Receptor Agonist ◽  
Activity Rhythm ◽  
Circadian System ◽  
Circadian Rhythmicity ◽  
Phase Shifting ◽  
Phase Resetting ◽  
Serotonin Agonist ◽  
Age Related ◽  
Temporal Adaptation ◽  
Circadian Time

Serotonergic mechanisms are believed to play a considerable role in mediating the effects of photic and nonphotic stimuli on circadian rhythmicity. Because aging is associated with significant changes in the responsiveness of the rodent circadian system to major synchronizing agents in the environment, this study examined the phase-shifting effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT; 2.0, 5.0, and 8.0 mg/kg ip at circadian time 8 (CT 8)], on the 24-h activity rhythm of young (3-4 mo old) and old (18-19 mo old) golden hamsters. Aging was associated with a dramatic attenuation of the phase-shifting effects of 8-OH-DPAT in this species. The results suggest the existence of age-related deficits in the serotonergic control of mammalian circadian rhythmicity, which could interfere with the temporal adaptation of the senescent organism to its environment.

Platelet Aggregation Induced in Vitro by Therapeutic Ultrasound

1977 ◽  
Vol 38 (03) ◽  
pp. 0640-0651 ◽  
Author(s):  
B. V Chater ◽  
A. R Williams
Keyword(s):  
Platelet Aggregation ◽  
Direct Action ◽  
Adenosine Diphosphate ◽  
Ultrasonic Cavitation ◽  
Related Phenomenon ◽  
Release Reaction ◽  
Physical Conditions ◽  
Platelet Aggregates ◽  
Active Substances

SummaryPlatelets were found to aggregate spontaneously when exposed to ultrasound generated by a commercial therapeutic device. At a given frequency, aggregation was found to be a dose-related phenomenon, increasing intensities of ultrasound inducing more extensive and more rapid aggregation. At any single intensity, the extent aggregation was increased as the frequency of the applied ultrasound was decreased (from 3.0 to 0.75 MHz).Ultrasound-induced platelet aggregation was found to be related to overall platelet sensitivity to adenosine diphosphate. More sensitive platelets were found to aggregate spontaneously at lower intensities of sound, and also the maximum extent of aggregation was found to be greater. Examination of ultrasound-induced platelet aggregates by electron microscopy demonstrated that the platelets had undergone the release reaction.The observation that haemoglobin was released from erythrocytes in whole blood irradiated under identical physical conditions suggests that the platelets are being distrupted by ultrasonic cavitation (violent gas/bubble oscillation).It is postulated that overall platelet aggregation is the result of two distinct effects. Firstly, the direct action of ultrasonic cavitation disrupts a small proportion of the platelet population, resulting in the liberation of active substances. These substances produce aggregation, both directly and indirectly by inducing the physiological release reaction in adjacent undamaged platelets.

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