scholarly journals The master clock and its timing of hormonal release

2011 ◽  
Vol 2 ◽  
Author(s):  
Wotus Cheryl
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Martin Deschênes ◽  
Anastasia Kurnikova ◽  
Michael Elbaz ◽  
David Kleinfeld

The exploratory behavior of rodents is characterized by stereotypical movements of the vibrissae, nose, and head, which are phase locked with rapid respiration, that is, sniffing. Here we review the brainstem circuitry that coordinates these actions and propose that respiration may act as a master clock for binding orofacial inputs across different sensory modalities.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Percy Griffin ◽  
Patrick W Sheehan ◽  
Julie M Dimitry ◽  
Chun Guo ◽  
Michael F Kanan ◽  
...  

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, including C4b and C3, in the hippocampus. BMAL1 regulates expression of the transcriptional repressor REV-ERBα, and deletion of REV-ERBα causes increased expression of C4b transcript in neurons and astrocytes as well as C3 protein primarily in astrocytes. REV-ERBα deletion increased microglial phagocytosis of synapses and synapse loss in the CA3 region of the hippocampus. Finally, we observed diurnal variation in the degree of microglial synaptic phagocytosis which was antiphase to REV-ERBα expression. This daily variation in microglial synaptic phagocytosis was abrogated by global REV-ERBα deletion, which caused persistently elevated synaptic phagocytosis. This work uncovers the BMAL1-REV-ERBα axis as a regulator of complement expression and synaptic phagocytosis in the brain, linking circadian proteins to synaptic regulation.


Author(s):  
Paul de Goede ◽  
Satish Sen ◽  
Yan Su ◽  
Ewout Foppen ◽  
Vincet-Joseph Poirel ◽  
...  

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.


BJPsych Open ◽  
2021 ◽  
Vol 7 (6) ◽  
Author(s):  
Havard Kallestad ◽  
Jan Scott

Summary The challenge of identifying efficacious out-patient treatments for depression is amplified by the increasing desire to find interventions that reduce the time to sustained improvement. One potential but underexplored option is triple chronotherapy (TCT). To date, use of TCT has been largely restricted to specialist units or in-patients. Recent research demonstrates that it may be possible to undertake sleep deprivation in out-patient settings, raising the possibility of delivering TCT to broader populations of individuals with depression. Emerging evidence suggests that out-patient TCT is a high-benefit, low-risk intervention but questions remain about how to target TCT and its mechanisms of action. Like traditional antidepressants, TCT probably acts through several pathways, especially the synchronisation of the ‘master clock’. Availability of reliable and valid methods of out-patient measurement of intra-individual circadian rhythmicity and light exposure are rate-limiting steps in the wider dissemination of TCT.


2018 ◽  
Author(s):  
Vikas Navratna ◽  
Dilip K. Tosh ◽  
Kenneth A. Jacobson ◽  
Eric Gouaux

AbstractThe human dopamine transporter(hDAT) plays a major role in dopamine homeostasis and regulation of neurotransmission by clearing dopamine from the extracellular space using secondary active transport. Dopamine is an essential monoamine chemical messenger that regulates reward seeking behavior, motor control, hormonal release, and emotional response in humans. Psychostimulants such as cocaine primarily target the central binding site of hDAT and lock the transporter in an outward-facing conformation, thereby inhibiting dopamine reuptake. The inhibition of dopamine reuptake leads to accumulation of dopamine in the synapse causing heightened signaling. In addition, hDAT is implicated in various neurological disorders and disease-associated neurodegeneration. Despite its significance, the molecular architecture of hDAT and its various conformational states are poorly understood. Instability of hDAT in detergent micelles has been a limiting factor in its successful biochemical, biophysical, and structural characterization. To overcome this hurdle, first we identified ligands that stabilize hDAT in detergent micelles. Then, we screened ∼200 single residue mutants of hDAT using high-throughput scintillation proximity assay, and identified a thermostable variant(I248Y). Here we report a robust strategy to overexpress and successfully purify a thermostable variant of hDAT in an inhibitor and allosteric ligand bound conformation.


1996 ◽  
Vol 31 (12) ◽  
pp. 1881-1887 ◽  
Author(s):  
T. Kwan ◽  
R. Adams ◽  
R. Libert
Keyword(s):  

2020 ◽  
pp. 3906-3913
Author(s):  
Eva Boonen ◽  
Greet Van den Berghe

Critical illness, an extreme form of severe physical stress, is characterized by important endocrine and metabolic changes. The development of critical care medicine has made possible survival from conditions that were previously rapidly fatel, and as a result many patients now enter a prolonged phase of chronic or persistent critical illness. Acute endocrine adaptations are directed towards providing energy and substrates for the vital fight or flight response in the context of exogenous substrate deprivation. Distinct endocrine and metabolic alterations characterize the chronic phase of critical illness, which seems to no longer be solely beneficial and may hamper recovery and rehabilitation. Onset of the stressful event causes an acute activation of pulsatile hormonal release from the anterior pituitary, followed by suppression in the chronic phase of illness, ultimately resolving to normality if recovery occurs.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryo Imai ◽  
Hiroshi Makino ◽  
Takasumi Katoh ◽  
Tetsuro Kimura ◽  
Tadayoshi Kurita ◽  
...  

Abstract Desflurane is one of the most frequently used inhalational anesthetics in clinical practice. A circadian rhythm phase-shift after general anesthesia with sevoflurane or isoflurane has been reported in mice, but few studies have reported this effect with desflurane. In the present study, we examined the rest/activity rhythm of mice by counting the number of running wheel rotations, and we found that desflurane anesthesia caused a phase shift in the circadian rhythm that was dependent on the time of day of anesthesia. We also found that desflurane anesthesia altered the relative mRNA expression of four major clock genes (Per2, Bmal, Clock, and Cry1) in the suprachiasmatic nucleus (SCN). These results are important for elucidating the effects of desflurane on the SCN, which is the master clock for the mammalian circadian rhythm. Further studies on the relationship between anesthesia and circadian rhythm may lead to the prevention and treatment of postoperative complications related to circadian rhythms.


2019 ◽  
Vol 20 (11) ◽  
pp. 2765 ◽  
Author(s):  
Jihwan Myung ◽  
Mei-Yi Wu ◽  
Chun-Ya Lee ◽  
Amalia Ridla Rahim ◽  
Vuong Hung Truong ◽  
...  

The kidney harbors one of the strongest circadian clocks in the body. Kidney failure has long been known to cause circadian sleep disturbances. Using an adenine-induced model of chronic kidney disease (CKD) in mice, we probe the possibility that such sleep disturbances originate from aberrant circadian rhythms in kidney. Under the CKD condition, mice developed unstable behavioral circadian rhythms. When observed in isolation in vitro, the pacing of the master clock, the suprachiasmatic nucleus (SCN), remained uncompromised, while the kidney clock became a less robust circadian oscillator with a longer period. We find this analogous to the silencing of a strong slave clock in the brain, the choroid plexus, which alters the pacing of the SCN. We propose that the kidney also contributes to overall circadian timekeeping at the whole-body level, through bottom-up feedback in the hierarchical structure of the mammalian circadian clocks.


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