scholarly journals The Impact of Sleep and Circadian Disturbance on Hormones and Metabolism

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tae Won Kim ◽  
Jong-Hyun Jeong ◽  
Seung-Chul Hong
Keyword(s):  
Clock Gene ◽  
Clock Genes ◽  
Circadian System ◽  
Lipid Homeostasis ◽  
Dark Cycle ◽  
Hormonal Imbalance ◽  
Glucose And Lipid Homeostasis ◽  
Highly Correlated ◽  
The Impact ◽  
Insulin Insensitivity

The levels of several hormones fluctuate according to the light and dark cycle and are also affected by sleep, feeding, and general behavior. The regulation and metabolism of several hormones are influenced by interactions between the effects of sleep and the intrinsic circadian system; growth hormone, melatonin, cortisol, leptin, and ghrelin levels are highly correlated with sleep and circadian rhythmicity. There are also endogenous circadian mechanisms that serve to regulate glucose metabolism and similar rhythms pertaining to lipid metabolism, regulated through the actions of various clock genes. Sleep disturbance, which negatively impacts hormonal rhythms and metabolism, is also associated with obesity, insulin insensitivity, diabetes, hormonal imbalance, and appetite dysregulation. Circadian disruption, typically induced by shift work, may negatively impact health due to impaired glucose and lipid homeostasis, reversed melatonin and cortisol rhythms, and loss of clock gene rhythmicity.

“Temporal control of tumor growth in nocturnal mammals: impact of the circadian system”

2020 ◽  
Author(s):  
Paula M. Wagner ◽  
César G. Prucca ◽  
Fabiola N. Velázquez ◽  
Lucas Sosa Alderete ◽  
Beatriz L. Caputto ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Clock Gene ◽  
Drug Efficacy ◽  
Circadian System ◽  
Tumor Formation ◽  
Constant Darkness ◽  
Nerve Sheath Tumor ◽  
Temporal Control ◽  
Dark Cycle ◽  
The Impact

AbstractGlioblastoma multiforme is the most aggressive brain tumor; however, little is known about the impact of the circadian system on the tumor formation, growth and treatment. We investigated day/night differences in tumor growth after injecting A530 glioma cells isolated from malignant peripheral nerve sheath tumor of NPcis (Trp53+/-; Nf1+/-) mice. Tumors generated in the sciatic nerve zone of C57BL/6 mice injected early at night in the light/dark cycle or in constant darkness, showed higher growth rates than in animals injected diurnally. Similar nocturnal increases were observed when injecting B16 melanoma cells or when mice received knocked-down clock gene Bmal1 cells. Moreover, treatment with a low-dose of the proteasome inhibitor Bortezomib (0.5 mg/kg) in tumor-bearing animals, displayed higher efficacy when administered at night. Results suggest the existence of a precise temporal control of tumor growth and of drug efficacy in which the host state and susceptibility are critical.

Clock Genes Disruption in the Intensive Care Unit

2019 ◽  
Vol 35 (12) ◽  
pp. 1497-1504
Author(s):  
Elena Diaz ◽  
Irene Diaz ◽  
Cecilia del Busto ◽  
Dolores Escudero ◽  
Silvia Pérez
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Mrna Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Biological Clock ◽  
Icu Patients ◽  
Time Points ◽  
Icu Stay ◽  
The Impact

Background: Intensive care unit (ICU) environment disrupts the circadian rhythms due to environmental and other nonphotic synchronizers. The main purpose of this article is to establish whether critically patients have desynchronization at the molecular level after 1 week of stay in the ICU. Methods: The rhythm of Clock, Bmal1, Cry1, and Per2 genes in neuro-ICU patients (n = 11) on the first day after admission in the unit (1 day) and 1 week later (1 week) was studied, 4 time points throughout the day, at 6, 12, 18, and 24 hours. Human whole blood samples were obtained from neuro-ICU patients. The total RNA was isolated and each sample was reverse transcribed to complementary DNA and quantitative polymerase chain reaction (PCRq) was performed. The possible rhythm was studied using Fourier Series. Results: After 1 week, the clock gene rhythmicity completely disappeared. Messenger RNA (mRNA) expression for the 4 clock genes was shown rhythmicity at the first day after admission in the ICU. Circadian rhythmicity for none of them was observed but rather, ultradian rhythmicity was found. The expression of Clock, Bmal1, and Per2 mRNA after 1 week was similar in the 4-time point studies without significant fluctuation among the 4 time points analyzed. Discussion: Rhythmic mRNA expression is present at the first day after admission in the ICU. However, ICU stay during 1 week affects the molecular machinery of the biological clock generating chronodisruption. Circadian disruption is associated with the risk of several pathologies, thus, it seems to be clear that ICU stay in constant conditions could adversely affect patient evolution and probably, circadian resynchronization restoring clock gene expression could lead to a better clinical evolution of the patient. Conclusions: Clock genes disruption is observed in neuro-ICU patients. Light therapy as well as melatonin treatment could reduce the impact of ICU stay period in biological clock, thereby improving patients’ recovery.

scholarly journals Shift Work, Jet Lag, and Female Reproduction

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Megan M. Mahoney
Keyword(s):  
Gene Expression ◽  
Shift Work ◽  
Clock Gene ◽  
Clock Genes ◽  
Reproductive Function ◽  
Jet Lag ◽  
Female Reproduction ◽  
Clock Gene Expression ◽  
Increased Risk ◽  
The Impact

Circadian rhythms and “clock gene” expression are involved in successful reproductive cycles, mating, and pregnancy. Alterations or disruptions of biological rhythms, as commonly occurs in shift work, jet lag, sleep deprivation, or clock gene knock out models, are linked to significant disruptions in reproductive function. These impairments include altered hormonal secretion patterns, reduced conception rates, increased miscarriage rates and an increased risk of breast cancer. Female health may be particularly susceptible to the impact of desynchronizing work schedules as perturbed hormonal rhythms can further influence the expression patterns of clock genes. Estrogen modifies clock gene expression in the uterus, ovaries, and suprachiasmatic nucleus, the site of the primary circadian clock mechanism. Further work investigating clock genes, light exposure, ovarian hormones, and reproductive function will be critical for indentifying how these factors interact to impact health and susceptibility to disease.

scholarly journals CLOCK Genes and Circadian Rhythmicity in Alzheimer Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
J. Thome ◽  
A. N. Coogan ◽  
A. G. Woods ◽  
C. C. Darie ◽  
F. Häßler
Keyword(s):  
Alzheimer Disease ◽  
Clock Gene ◽  
Clock Genes ◽  
Sleep Problems ◽  
Internal Clock ◽  
Circadian Rhythmicity ◽  
Clock Gene Expression ◽  
Endogenous Clock ◽  
Exogenous Factors ◽  
The Impact

Disturbed circadian rhythms with sleep problems and disrupted diurnal activity are often seen in patients suffering from Alzheimer disease (AD). Both endogenous CLOCK genes and external Zeitgeber are responsible for the maintenance of circadian rhythmicity in humans. Therefore, modifications of the internal CLOCK system and its interactions with exogenous factors might constitute the neurobiological basis for clinically observed disruptions in rhythmicity, which often have grave consequences for the quality of life of patients and their caregivers. Presently, more and more data are emerging demonstrating how alterations of the CLOCK gene system might contribute to the pathophysiology of AD and other forms of dementia. At the same time, the impact of neuropsychiatric medication on CLOCK gene expression is under investigation.

scholarly journals The Lack of Light-Dark and Feeding-Fasting Cycles Alters Temporal Events in the Goldfish (Carassius auratus) Stress Axis

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 669
Author(s):  
Nuria Saiz ◽  
Miguel Gómez-Boronat ◽  
Nuria De Pedro ◽  
María Jesús Delgado ◽  
Esther Isorna
Keyword(s):  
Clock Gene ◽  
Environmental Changes ◽  
Clock Genes ◽  
Stress Axis ◽  
Constant Darkness ◽  
Dark Cycle ◽  
Goldfish Carassius Auratus ◽  
Clock Gene Expression ◽  
Temporal Events ◽  
Cortisol Release

Vertebrates possess circadian clocks, driven by transcriptional–translational loops of clock genes, to orchestrate anticipatory physiological adaptations to cyclic environmental changes. This work aims to investigate how the absence of a light-dark cycle and a feeding schedule impacts the oscillators in the hypothalamus-pituitary-interrenal axis of goldfish. Fish were maintained under 12L:12D feeding at ZT 2; 12L:12D feeding at random times; and constant darkness feeding at ZT 2. After 30 days, fish were sampled to measure daily variations in plasma cortisol and clock gene expression in the hypothalamus-pituitary-interrenal (HPI) axis. Clock gene rhythms in the HPI were synchronic in the presence of a light-dark cycle but were lost in its absence, while in randomly fed fish, only the interrenal clock was disrupted. The highest cortisol levels were found in the randomly fed group, suggesting that uncertainty of food availability could be as stressful as the absence of a light-dark cycle. Cortisol daily rhythms seem to depend on central clocks, as a disruption in the adrenal clock did not impede rhythmic cortisol release, although it could sensitize the tissue to stress.

Reproductive performance in female ClockΔ19 mutant mice

2004 ◽  
Vol 16 (8) ◽  
pp. 801 ◽  
Author(s):  
David J. Kennaway ◽  
Michael J. Boden ◽  
Athena Voultsios
Keyword(s):  
Reproductive Performance ◽  
Gene Function ◽  
Clock Gene ◽  
Circadian System ◽  
Mutant Mice ◽  
Constant Darkness ◽  
Control Line ◽  
Cba Mice ◽  
The Impact ◽  
The Relationship

The relationship between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been well established. The present study evaluated the reproductive performance of mice carrying the ClockΔ19 mutation that were either melatonin deficient (ClockΔ19/Δ19) or had the capacity to synthesise melatonin reinstated (ClockΔ19/Δ19+MEL). The ClockΔ19/Δ19 mice took 2–3 days longer to mate, and to subsequently deliver pups, than their control line. The melatonin-competent mutants had a smaller, but still significant (P < 0.05), delay. The ClockΔ19 mutation resulted in smaller median litter sizes compared with control lines (seven v. eight pups; P < 0.05), whereas melatonin proficiency reversed this difference. Survival to weaning was 84% and 80% for the ClockΔ19/Δ19 and ClockΔ19/Δ19+MEL lines, respectively, compared with 94–96% for the two control lines. The ClockΔ19/Δ19 mutants became behaviourally arrhythmic in constant darkness but, despite this, seven of seven became pregnant when paired with males after at least 14 days of constant darkness (five of seven within 4 days of pairing). In the ClockΔ19/Δ19+MEL mice, seven of 15 became arrhythmic in constant darkness but still became pregnant. The seven mice that free ran for at least 14 days in constant darkness with a period of 27.1 h also became pregnant. The present study has demonstrated that the ClockΔ19 mutation has significant, but subtle, effects on reproductive performance. The reintroduction of melatonin competency and/or other genes as a result of crosses with CBA mice reduced the impact of the mutation further. It would appear that redundancy in genes in the circadian system allows the reproductive cyclicity to persist in mice, albeit at a suboptimal level.

scholarly journals Normalized coefficient of variation (nCV): a method to evaluate circadian clock robustness in population scale data

2021 ◽  
Author(s):  
Gang Wu ◽  
Lauren J. Francey ◽  
Marc D. Ruben ◽  
John B. Hogenesch
Keyword(s):  
Circadian Clock ◽  
Coefficient Of Variation ◽  
Therapeutic Target ◽  
Clock Gene ◽  
Clock Genes ◽  
Population Level ◽  
Circadian System ◽  
Core Feature ◽  
Population Scale ◽  
Scale Data

Robust oscillation of clock genes is a core feature of the circadian system. Relative amplitude (rAMP) measures the robustness of clock gene oscillations, but only works for longitudinal samples. We lack a method for estimating robust oscillations from human samples without labeled time. We show that the normalized coefficient of variation (nCV) is linearly correlated with rAMP, independent of time labels. Using nCV, we found that clock gene oscillations are consistently dampened in tumors compared to non-tumors, suggesting a new therapeutic target in cancer treatment by enhancing clock robustness. nCV can provide a simple measure of the robustness of clock gene oscillations in any population-level dataset.

scholarly journals Genome-wide correlation analysis to identify amplitude regulators of circadian transcriptome output

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Evan S. Littleton ◽  
Madison L. Childress ◽  
Michaela L. Gosting ◽  
Ayana N. Jackson ◽  
Shihoko Kojima
Keyword(s):  
Clock Genes ◽  
Circadian System ◽  
Average Level ◽  
Relative Amplitude ◽  
Critical Component ◽  
Period 2 ◽  
Genome Wide ◽  
Mouse Tissues ◽  
Rhythmic Gene ◽  
Insight Into

AbstractCell-autonomous circadian system, consisting of core clock genes, generates near 24-h rhythms and regulates the downstream rhythmic gene expression. While it has become clear that the percentage of rhythmic genes varies among mouse tissues, it remains unclear how this variation can be generated, particularly when the clock machinery is nearly identical in all tissues. In this study, we sought to characterize circadian transcriptome datasets that are publicly available and identify the critical component(s) involved in creating this variation. We found that the relative amplitude of 13 genes and the average level of 197 genes correlated with the percentage of cycling genes. Of those, the correlation of Rorc in both relative amplitude and the average level was one of the strongest. In addition, the level of Per2AS, a novel non-coding transcript that is expressed at the Period 2 locus, was also linearly correlated, although with a much lesser degree compared to Rorc. Overall, our study provides insight into how the variation in the percentage of clock-controlled genes can be generated in mouse tissues and suggests that Rorc and potentially Per2AS are involved in regulating the amplitude of circadian transcriptome output.

scholarly journals Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna A. Lauer ◽  
Daniel Janitschke ◽  
Malena dos Santos Guilherme ◽  
Vu Thu Thuy Nguyen ◽  
Cornel M. Bachmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Lipid Homeostasis ◽  
Medical Surveillance ◽  
Shotgun Lipidomics ◽  
App Processing ◽  
Cognitive Improvement ◽  
The Impact

AbstractAlzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients.

scholarly journals The Influence of Trading Locations on Equity Returns

2016 ◽  
Vol 12 (12) ◽  
pp. 188
Author(s):  
Nguyen N.T. Vo
Keyword(s):  
Risk Premium ◽  
Stock Price ◽  
Listed Companies ◽  
Equity Returns ◽  
Stock Exchanges ◽  
Home Market ◽  
Trade Effect ◽  
Market Index ◽  
Highly Correlated ◽  
The Impact

This paper evaluates the impact of trading locations on equity returns by examining the stock price behaviour of three Anglo-Dutch dual-listed companies which result from mergers where two corporations agree to function as a single operating business, but maintain separate identities. The shares of these stocks are traded not only in their home market but also on several US stock exchanges in the form of American Depository Receipts. Regressing the return differentials on these dual-listed and cross-listed stocks on the relative market index returns and currency changes provides evidence of an apparent violation of the Law of One Price. The regression results show that the return on each part of dual-listed companies is highly correlated with the market on which it is most intensively traded. Similarly, returns on cross-listed stocks have considerably higher co-movement with US market indices and considerably lower co-movement with home-market indices than their home-market counterparts. Market risk premium is not a significant explanatory variable of the location of trade effect.

Sign in / Sign up

Export Citation Format

Share Document