Cycloheximide-induced phase shifting of circadian clock of Neurospora

1981 ◽  
Vol 241 (1) ◽  
pp. R31-R35 ◽  
Author(s):  
H. Nakashima ◽  
J. Perlman ◽  
J. F. Feldman
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Response Curve ◽  
Phase Response Curve ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Normal Operation ◽  
Circadian Cycle ◽  
Response Curves ◽  
Inhibition Of Protein Synthesis

Cycloheximide (CHX), an inhibitor of cytosolic (80S) protein synthesis in eucaryotes, causes phase shifts of the circadian clock of Neurospora crassa when administered as 4-h pulses to cultures in liquid medium. Differential effects of the pulses at different phases of the circadian cycle were observed and plotted as a phase-response curve (PRC). Nearly all phase shifts observed were phase advances, with maximum sensitivity in the middle of the subjective day. Inhibition of protein synthesis by CHX was the same at both phases of the cycle. The PRC was the same at 20 and 25 degrees C. Dose-response curves for the effects of CHX on phase shifting and inhibition of protein synthesis were determined and showed a striking parallel in the responses of these two phenomena to CHX. These results support the view that synthesis of one or more proteins at specific phases of the circadian cycle is necessary for the normal operation of the circadian clock of Neurospora.

Involvement of protein synthesis in circadian clock of Aplysia eye

1986 ◽  
Vol 250 (1) ◽  
pp. R5-R17
Author(s):  
D. P. Lotshaw ◽  
J. W. Jacklet
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Response Curve ◽  
Phase Response Curve ◽  
Phase Shifting ◽  
Protein Synthesis Inhibition ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibition ◽  
Subjective Night ◽  
Induce Phase

The effects of the protein synthesis inhibitors anisomycin and puromycin were measured on protein synthesis and phase shifting of the circadian rhythm in the isolated Aplysia eye. Anisomycin pulses induce phase delays proportional in magnitude to the duration and percentage of protein synthesis inhibition. The phase-response curve to anisomycin pulses consisted of delays induced throughout the subjective night. Delays were maximal between circadian times (CT) 18 and CT 2; pulses initiated between CT 2 and CT 12 did not phase shift. Puromycin induced phase delays and advances. Delays were proportional to the duration and percentage of protein synthesis inhibition, occurring with increasing magnitude throughout the subjective night (CT 12-2). Peptidyl-puromycin formation may contribute to the magnitude of the delay. Advances, occurring between CT 2 and CT 8, required a greater drug concentration and pulse duration than delays and appeared to result from an effect other than protein synthesis inhibition. Our results support the hypothesis of a phase-dependent requirement for protein synthesis during the subjective night in this circadian clock.

Glucocorticosteroid injection is a circadian zeitgeber in the laboratory rat

1982 ◽  
Vol 243 (3) ◽  
pp. R373-R378 ◽  
Author(s):  
N. D. Horseman ◽  
C. F. Ehret
Keyword(s):  
Phase Response Curve ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Constant Darkness ◽  
Circadian Cycle ◽  
Saline Injection ◽  
Laboratory Rats ◽  
Circadian Phase ◽  
Ad Libitum Feeding

Intraperitoneal temperatures were monitored by radiotelemetry to observe the thermoregulatory rhythm of male laboratory rats (Rattus norvegicus albinus) Rats received single injections of dexamethasone (as dexamethasone sodium phosphate) during constant darkness (0.1 lx) with food freely available or no food available. No phase shifts occurred following saline injection or dexamethasone at 1 mg/kg body wt. Depending on the phase of injection relative to the circadian cycle, dexamethasone at 10 mg/kg caused thermoregulatory peaks to be either delayed or advanced on the 4th and 5th day after injection. There was an insensitive interval which corresponded to subjective day. Phase shifts induced by dexamethasone during ad libitum feeding were of less magnitude than those induced during starvation. The determination of phase-shifting parameters (i.e., a phase-response curve) for hormonal substances represents a rigorous and broadly applicable technique for determining endogenous mechanisms for circadian phase control and entrainment.

Inhibitors of protein synthesis on 80S ribosomes phase shift the Gonyaulax clock

1982 ◽  
Vol 97 (1) ◽  
pp. 121-136
Author(s):  
W. R. Taylor ◽  
J. C. Dunlap ◽  
J. W. Hastings
Keyword(s):  
Protein Synthesis ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Phase Shift ◽  
Phase Shifts ◽  
Circadian Cycle ◽  
Response Curves ◽  
80S Ribosome ◽  
Strong Phase ◽  
Additional Support

One-hour pulses of anisomycin (0.3 microM), streptimidone (30 microM) and cycloheximide (5 microM) caused strong phase-shifts (either advances or delays, of up to 12 h) in the circadian rhythm of the bioluminescence glow in the marine photosynthetic dinoflagellate, Gonyaulax polyedra. Similar pulses of emetine (0.1-100 microM) caused small (less than 4 h) phase shifts. Drug pulses have quantitatively different effects when applied at different phases of the circadian cycle, thus giving rise to ‘phase response curves’ (PRC's). The results lend additional support to the generalization, based on results from several different organisms, that 80s ribosome protein synthesizing system is of key importance in the mechanism responsible for circadian rhythms.

Entrainment of the circadian rhythm from the eye of Aplysia: role of serotonin

1982 ◽  
Vol 242 (3) ◽  
pp. R326-R332
Author(s):  
G. Corrent ◽  
A. Eskin ◽  
I. Kay
Keyword(s):  
Circadian Rhythm ◽  
Phase Shift ◽  
Transmitter Release ◽  
Response Curve ◽  
Phase Shifts ◽  
Phase Response ◽  
Phase Shifting ◽  
Response Curves ◽  
Light Pulses

The finding that serotonin (5-HT) treatments as short as 1.5 h in duration produce phase shifts in a circadian rhythm from the isolated eye of Aplysia suggested that release of 5-HT was part of an ocular entrainment pathway. Since light cycles entrain this rhythm, we compared phase shifting by 5-HT and by light. The similarity in the shapes of the phase-response curves for 5-HT and light pulses indicates that 5-HT treatments are capable of entraining the rhythm. Also, "skeleton" 5-HT treatments phase shift as well as continuous 5-HT treatments. However, 5-HT does not appear to mediate the phase shifts produced by light, since 1) treatments that should block transmitter release do not change the phase shifts produced by light pulses; 2) the response curves of 5-HT and light pulses are displaced by 12 h relative to one another on the phase axis of the response curve; and 3) light-induced phase shifts are apparent almost immediately, whereas 5-HT-induced phase shifts become evident only about 24 h after 5-HT treatment. The eye appears to contain two independent entrainment pathways, one for light and one utilizing 5-HT.

scholarly journals General Anaesthesia Shifts the Murine Circadian Clock in a Time-Dependant Fashion

2021 ◽  
Vol 3 (1) ◽  
pp. 87-97
Author(s):  
Nicola M. Ludin ◽  
Alma Orts-Sebastian ◽  
James F. Cheeseman ◽  
Janelle Chong ◽  
Alan F. Merry ◽  
...  
Keyword(s):  
Circadian Clock ◽  
General Anaesthesia ◽  
Wheel Running ◽  
Phase Shifts ◽  
Time Dependent ◽  
Suprachiasmatic Nuclei ◽  
Response Curves ◽  
Inhalational Anaesthetic ◽  
Locomotor Rhythms ◽  
Time Dependent Analysis

Following general anaesthesia (GA), patients frequently experience sleep disruption and fatigue, which has been hypothesized to result at least in part by GA affecting the circadian clock. Here, we provide the first comprehensive time-dependent analysis of the effects of the commonly administered inhalational anaesthetic, isoflurane, on the murine circadian clock, by analysing its effects on (a) behavioural locomotor rhythms and (b) PER2::LUC expression in the suprachiasmatic nuclei (SCN) of the mouse brain. Behavioural phase shifts elicited by exposure of mice (n = 80) to six hours of GA (2% isoflurane) were determined by recording wheel-running rhythms in constant conditions (DD). Phase shifts in PER2::LUC expression were determined by recording bioluminescence in organotypic SCN slices (n = 38) prior to and following GA exposure (2% isoflurane). Full phase response curves for the effects of GA on behaviour and PER2::LUC rhythms were constructed, which show that the effects of GA are highly time-dependent. Shifts in SCN PER2 expression were much larger than those of behaviour (c. 0.7 h behaviour vs. 7.5 h PER2::LUC). We discuss the implications of this work for understanding how GA affects the clock, and how it may inform the development of chronotherapeutic strategies to reduce GA-induced phase-shifting in patients.

scholarly journals PDF neuron firing phase-shifts key circadian activity neurons in Drosophila

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Fang Guo ◽  
Isadora Cerullo ◽  
Xiao Chen ◽  
Michael Rosbash
Keyword(s):  
Response Curve ◽  
Phase Response Curve ◽  
Receptor Expression ◽  
Phase Shifting ◽  
Constant Darkness ◽  
Behavioral Rhythms ◽  
Circadian Phase ◽  
Phase Adjustment ◽  
Drosophila Brain ◽  
A Cell

Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.

Protein synthesis requirement of the Aplysia circadian clock. Tested by active and inactive derivatives of the inhibitor anisomycin

1980 ◽  
Vol 85 (1) ◽  
pp. 33-42
Author(s):  
J. W. Jacklet
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Compound Action Potential ◽  
Phase Shifts ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Inhibitor Molecule ◽  
Group 5 ◽  
Characteristic Effect ◽  
Derivatives Of

1.The circadian rhythm of compound action potential frequency recorded from the isolated eye of Aplysia in culture medium and darkness was subjected to 6 h pulse treatments with either anisomycin, a protein synthesis inhibitor, or inactive derivatives of anisomycin. 2. Anisomycin caused phase-dependent phase shifts of the rhythm as expected from previous experiments, but none of the derivative molecules caused phase shifts or perturbed the rhythm. 3. Anisomycin inhibited eye-protein synthesis by 75% at the concentrations (10(−6) M) used in the phase shifting experiments but none of the derivatives inhibited synthesis. 4. Only those molecules that actually inhibited protein synthesis caused phase shifts of the clock, although the inactive derivatives differed from anisomycin by only an acetyl group. 5. The results strengthen the conclusion that the inhibition of protein synthesis caused by anisomycin is important in perturbing the timing of the circadian clock and not some other characteristic effect of the inhibitor molecule. Together with the results from other systems, these findings imply that the daily synthesis of protein is a general requirement for circadian clocks.

Temperature Sensitive Events between Photoreceptor and Circadian Clock?

1975 ◽  
Vol 30 (3-4) ◽  
pp. 240-244 ◽  
Author(s):  
Ursula Hamm ◽  
M Aroli ◽  
K Chandrashekaran ◽  
W Olfgang Engelmann
Keyword(s):  
Low Temperature ◽  
Response Curve ◽  
Time Course ◽  
Phase Response Curve ◽  
Phase Response ◽  
Phase Shifting ◽  
Wave Form ◽  
Temperature Sensitive ◽  
Slowing Down ◽  
Light Pulses

Abstract The phase shifting action of low temperature pulses of 6 °C and 2 h duration administered to the various phases of the Drosophila pseudoobscura circadian rhythm and the action of light pulses given 30 min after the beginning of these low temperature pulses have been investigated. The phase response curve obtained from experiments with light pulses during low temperature cannot be ex­ plained on the basis of a straightforward and sequential phase shifting of the oscillation by the various transitions in the pulses. The response curve, after the slight phase shifting action of the temperature pulses is corrected for, resembles the standard phase response curve 4 for light pulses (at 20 °C) in its wave form but not in its time course. Our curve is shifted in time in a manner that indicates that the light pulses accompanying the low temperature pulses arrived at phase points 1.5 h later than the actual phases at which they were given. We attribute this delay to a slowing down of the information that is apparently transmitted by a process that is temperature dependent.

Photoperiod differentially modulates photic and nonphotic phase response curves of hamsters

2004 ◽  
Vol 286 (3) ◽  
pp. R539-R546 ◽  
Author(s):  
J. A. Evans ◽  
J. A. Elliott ◽  
M. R. Gorman
Keyword(s):  
Wheel Running ◽  
Phase Response Curve ◽  
Phase Shifts ◽  
Phase Response ◽  
Cycle Phase ◽  
Phase Resetting ◽  
Response Curves ◽  
Syrian Hamsters ◽  
Light Pulses ◽  
Circadian Time

Circadian pacemakers respond to light pulses with phase adjustments that allow for daily synchronization to 24-h light-dark cycles. In Syrian hamsters, Mesocricetus auratus, light-induced phase shifts are larger after entrainment to short daylengths (e.g., 10 h light:14 h dark) vs. long daylengths (e.g., 14 h light:10 h dark). The present study assessed whether photoperiodic modulation of phase resetting magnitude extends to nonphotic perturbations of the circadian rhythm and, if so, whether the relationship parallels that of photic responses. Male Syrian hamsters, entrained for 31 days to either short or long daylengths, were transferred to novel wheel running cages for 2 h at times spanning the entire circadian cycle. Phase shifts induced by this stimulus varied with the circadian time of exposure, but the amplitude of the resulting phase response curve was not markedly influenced by photoperiod. Previously reported photoperiodic effects on photic phase resetting were verified under the current paradigm using 15-min light pulses. Photoperiodic modulation of phase resetting magnitude is input specific and may reflect alterations in the transmission of photic stimuli.

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