scholarly journals Evidence for a Putative Circadian Kiss-Clock in the Hypothalamic AVPV in Female Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (8) ◽  
pp. 2999-3011 ◽  
Author(s):  
David Chassard ◽  
Isabelle Bur ◽  
Vincent-Joseph Poirel ◽  
Jorge Mendoza ◽  
Valérie Simonneaux
Keyword(s):  
Circadian Clock ◽  
Time Of Day ◽  
Daily Rhythm ◽  
Circadian Period ◽  
Suprachiasmatic Nuclei ◽  
Intact Female ◽  
Lh Surge ◽  
Female Mice ◽  
Periventricular Nucleus ◽  
Clock Protein

Abstract The kisspeptin (Kp) neurons in the anteroventral periventricular nucleus (AVPV) are essential for the preovulatory LH surge, which is gated by circulating estradiol (E2) and the time of day. We investigated whether AVPV Kp neurons in intact female mice may be the site in which both E2 and daily signals are integrated and whether these neurons may host a circadian oscillator involved in the timed LH surge. In the afternoon of proestrous day, Kp immunoreactivity displayed a marked and transient decrease 2 hours before the LH surge. In contrast, Kp content was stable throughout the day of diestrus, when LH levels are constantly low. AVPV Kp neurons expressed the clock protein period 1 (PER1) with a daily rhythm that is phase delayed compared with the PER1 rhythm measured in the main clock of the suprachiasmatic nuclei (SCN). PER1 rhythm in the AVPV, but not in the SCN, exhibited a significant phase delay of 2.8 hours in diestrus as compared with proestrus. Isolated Kp-expressing AVPV explants from PER2::LUCIFERASE mice displayed sustained circadian oscillations of bioluminescence with a circadian period (23.2 h) significantly shorter than that of SCN explants (24.5 h). Furthermore, in AVPV explants incubated with E2 (10 nM to 1 μM), the circadian period was lengthened by 1 hour, whereas the SCN clock remained unaltered. In conclusion, these findings indicate that AVPV Kp neurons display an E2-dependent daily rhythm, which may possibly be driven by an intrinsic circadian clock acting in combination with the SCN timing signal.

scholarly journals Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension

2019 ◽  
Vol 316 (1) ◽  
pp. R50-R58 ◽  
Author(s):  
Lauren G. Douma ◽  
Kristen Solocinski ◽  
Meaghan R. Holzworth ◽  
G. Ryan Crislip ◽  
Sarah H. Masten ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Clock ◽  
Dependent Manner ◽  
High Salt Diet ◽  
Female Mice ◽  
Night And Day ◽  
Long Acting ◽  
First Time ◽  
Cardiovascular Rhythms ◽  
Clock Protein

The circadian clock is integral to the maintenance of daily rhythms of many physiological outputs, including blood pressure. Our laboratory has previously demonstrated the importance of the clock protein period 1 (PER1) in blood pressure regulation in male mice. Briefly, a high-salt diet (HS; 4% NaCl) plus injection with the long-acting mineralocorticoid deoxycorticosterone pivalate (DOCP) resulted in nondipping hypertension [<10% difference between night and day blood pressure (BP) in Per1-knockout (KO) mice but not in wild-type (WT) mice]. To date, there have been no studies that have examined the effect of a core circadian gene KO on BP rhythms in female mice. The goal of the present study was to determine whether female Per1-KO mice develop nondipping hypertension in response to HS/DOCP treatment. For the first time, we demonstrate that loss of the circadian clock protein PER1 in female mice does not significantly change mean arterial pressure (MAP) or the BP rhythm relative to female C57BL/6 WT control mice. Both WT and Per1-KO female mice experienced a significant increase in MAP in response to HS/DOCP. Importantly, however, both genotypes maintained a >10% dip in BP on HS/DOCP. This effect is distinct from the nondipping hypertension seen in male Per1-KO mice, demonstrating that the female sex appears to be protective against PER1-mediated nondipping hypertension in response to HS/DOCP. Together, these data suggest that PER1 acts in a sex-dependent manner in the regulation of cardiovascular rhythms.

scholarly journals Circadian asthma airway responses are gated by REV-ERBα

2020 ◽  
pp. 1902407
Author(s):  
Hannah J. Durrington ◽  
Karolina Krakowiak ◽  
Peter Meijer ◽  
Nicola Begley ◽  
Robert Maidstone ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Airway Hyperresponsiveness ◽  
Ex Vivo ◽  
Allergen Challenge ◽  
Active Phase ◽  
Time Of Day ◽  
Receptor Expression ◽  
Dominant Feature ◽  
Clock Protein

BackgroundAsthma is an inflammatory disease of the airway showing a strong time of day rhythm. Airway hyperresponsiveness is a dominant feature of asthma, but it is not known if this is under clock control. The circadian clock powerfully regulates inflammation. The clock protein REV-ERBα is known to play a key role as a repressor of the inflammatory response.ObjectivesTo determine if allergy mediated airway hyperresponsiveness is gated by the clock protein, REV-ERBα.MethodsAfter exposure to the intra-nasal house dust mite allergen challenge model at either dawn or dusk, airway hyper-responsiveness to methacholine was measured invasively in mice.Main ResultsWild-type mice showed marked time-of-day differential responses of airway hyper-responsiveness (maximal at dusk, start of the active phase), both in vivo and ex vivo in precision cut lung slices. Hyper-responsive time of day effects were abolished in mice lacking the clock gene Rev-erbα, indicating that time-of-day effects on asthma responses are likely mediated via the circadian clock. We suggest that muscarinic receptors 1 and 3 (Chrm 1, 3) may play a role in this pathway.ConclusionsWe identify a novel circuit regulating a core process in asthma, potentially involving circadian control of muscarinic receptor expression, in a REV-ERBα dependent fashion.Clinical ImplicationThese insights suggest the importance of considering timing of drug administration in clinic trials, and in clinical practice; chronotherapy.

scholarly journals Decoupling circadian clock protein turnover from circadian period determination

Science ◽  
2015 ◽  
Vol 347 (6221) ◽  
pp. 1257277-1257277 ◽  
Author(s):  
L. F. Larrondo ◽  
C. Olivares-Yanez ◽  
C. L. Baker ◽  
J. J. Loros ◽  
J. C. Dunlap
Keyword(s):  
Circadian Clock ◽  
Protein Turnover ◽  
Circadian Period ◽  
Clock Protein

scholarly journals Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA

2018 ◽  
Author(s):  
David G. Welkie ◽  
Benjamin E. Rubin ◽  
Yong-Gang Chang ◽  
Spencer Diamond ◽  
Scott A. Rifkin ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Environmental Changes ◽  
Time Of Day ◽  
Negative Regulator ◽  
Starvation Period ◽  
Night Time ◽  
Photosynthetic Organisms ◽  
Genetic Components ◽  
Clock Protein

AbstractThe recurrent pattern of light and darkness generated by Earth’s axial rotation has profoundly influenced the evolution of organisms, selecting for both biological mechanisms that respond acutely to environmental changes and circadian clocks that program physiology in anticipation of daily variations. The necessity to integrate environmental responsiveness and circadian programming is exemplified in photosynthetic organisms such as cyanobacteria, which depend on light-driven photochemical processes. The cyanobacterium Synechococcus elongatus PCC 7942 is an excellent model system for dissecting these entwined mechanisms. Its core circadian oscillator, consisting of three proteins KaiA, KaiB, and KaiC, transmits time-of-day signals to clock-output proteins, which reciprocally regulate global transcription. Research performed under constant light facilitates analysis of intrinsic cycles separately from direct environmental responses, but does not provide insight into how these regulatory systems are integrated during light-dark cycles. Thus, we sought to identify genes that are specifically necessary in a day-night environment. We screened a dense bar-coded transposon library in both continuous light and daily cycling conditions and compared the fitness consequences of loss of each nonessential gene in the genome. Although the clock itself is not essential for viability in light-dark cycles, the most detrimental mutations revealed by the screen were those that disrupt KaiA. The screen broadened our understanding of light-dark survival in photosynthetic organisms, identified unforeseen clock-protein interaction dynamics, and reinforced the role of the clock as a negative regulator of a night-time metabolic program that is essential for S. elongatus to survive in the dark.SignificanceUnderstanding how photosynthetic bacteria respond to and anticipate natural light–dark cycles is necessary for predictive modeling, bioengineering, and elucidating metabolic strategies for diurnal growth. Here, we identify the genetic components that are important specifically under light-dark cycling conditions and determine how a properly functioning circadian clock prepares metabolism for darkness, a starvation period for photoautotrophs. This study establishes that the core circadian clock protein KaiA is necessary to enable rhythmic de-repression of a night-time circadian program.

scholarly journals The Dorsomedial Suprachiasmatic Nucleus Times Circadian Expression of Kiss1 and the Luteinizing Hormone Surge

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2839-2850 ◽  
Author(s):  
Benjamin L. Smarr ◽  
Emma Morris ◽  
Horacio O. de la Iglesia
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Phase Coherence ◽  
Reproductive Disorders ◽  
Lh Surge ◽  
Circadian Expression ◽  
Neural Input ◽  
Periventricular Nucleus ◽  
Gnrh Neurons ◽  
Neuronal Oscillators

Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic nucleus (SCN). GnRH neurons represent the converging pathway through which the brain triggers ovulation, but precisely how the SCN times GnRH neurons is unknown. We tested the hypothesis that neurons expressing kisspeptin, a neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH cells during ovulation, represent a relay station for circadian information that times ovulation. We first show that the circadian increase of Kiss1 expression, as well as the activation of GnRH cells, relies on intact ipsilateral neural input from the SCN. Second, by desynchronizing the dorsomedial (dm) and ventrolateral (vl) subregions of the SCN, we show that a clock residing in the dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1 expression in the anteroventral periventricular nucleus of the hypothalamus and that this rhythm is always in phase with the LH surge. In addition, we show that although the timing of the LH surge is governed by the dmSCN, its amplitude likely depends on the phase coherence between the vlSCN and dmSCN. Our results suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH surge through input to kisspeptin cells in the anteroventral periventricular nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra-SCN oscillators is critical for shaping it. They also suggest that female reproductive disorders associated with nocturnal shift work could emerge from the desynchronization between subregional oscillators within the master circadian clock.

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.

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