Sleep Optimization

2019 ◽  
pp. 127-146
Author(s):  
Lyn Freeman
Keyword(s):  
Circadian Rhythms ◽  
Sleep Deprivation ◽  
Motivational Interviewing ◽  
Patient Population ◽  
Clock Genes ◽  
Sleep Hygiene ◽  
Frame Of Reference ◽  
What Works ◽  
Pain Patients

Sleep deprivation is arguably the single most compromising event that prevents pain patients from changing behavior. To get the sleep-deprived patient to take action to improve their sleep and become more capable of healthy change, healthcare practitioners must approach the patient with the evidence of “what works,” but on his or her own terms, in a language that he or she can understand and cognitively retain, and in a psychological manner that will inspire hope and increase motivation. This chapter endeavors to accomplish the following: (1) review the scope of the problem; (2) clarify the frame of reference of the author; (3) explain how humans function as living rhythm machines; (4) define circadian rhythms, chronobiology, and clock genes; (5) describe the challenges of improving sleep hygiene in a patient population; and (6) identify the methods of change used clinically, including motivational interviewing.

scholarly journals Shared Components of the FRQ-Less Oscillator and TOR Pathway Maintain Rhythmicity in Neurospora

2021 ◽  
pp. 074873042199994
Author(s):  
Rosa Eskandari ◽  
Lalanthi Ratnayake ◽  
Patricia L. Lakin-Thomas
Keyword(s):  
Circadian Rhythms ◽  
Clock Genes ◽  
Nutrient Sensing ◽  
Mass Spectrometry Analysis ◽  
Growth Responses ◽  
Tor Pathway ◽  
Spectrometry Analysis ◽  
Binding Partner ◽  
Binding Partners ◽  
Free Running

Molecular models for the endogenous oscillators that drive circadian rhythms in eukaryotes center on rhythmic transcription/translation of a small number of “clock genes.” Although substantial evidence supports the concept that negative and positive transcription/translation feedback loops (TTFLs) are responsible for regulating the expression of these clock genes, certain rhythms in the filamentous fungus Neurospora crassa continue even when clock genes ( frq, wc-1, and wc-2) are not rhythmically expressed. Identification of the rhythmic processes operating outside of the TTFL has been a major unresolved area in circadian biology. Our lab previously identified a mutation ( vta) that abolishes FRQ-less rhythmicity of the conidiation rhythm and also affects rhythmicity when FRQ is functional. Further studies identified the vta gene product as a component of the TOR (Target of Rapamycin) nutrient-sensing pathway that is conserved in eukaryotes. We now report the discovery of TOR pathway components including GTR2 (homologous to the yeast protein Gtr2, and RAG C/D in mammals) as binding partners of VTA through co-immunoprecipitation (IP) and mass spectrometry analysis using a VTA-FLAG strain. Reciprocal IP with GTR2-FLAG found VTA as a binding partner. A Δ gtr2 strain was deficient in growth responses to amino acids. Free-running conidiation rhythms in a FRQ-less strain were abolished in Δ gtr2. Entrainment of a FRQ-less strain to cycles of heat pulses demonstrated that Δ gtr2 is defective in entrainment. In all of these assays, Δ gtr2 is similar to Δ vta. In addition, expression of GTR2 protein was found to be rhythmic across two circadian cycles, and functional VTA was required for GTR2 rhythmicity. FRQ protein exhibited the expected rhythm in the presence of GTR2 but the rhythmic level of FRQ dampened in the absence of GTR2. These results establish association of VTA with GTR2, and their role in maintaining functional circadian rhythms through the TOR pathway.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals Modulatory Effects of Circadian Rhythms in the Lung Adenocarcinoma Tumor Microenvironment

2021 ◽  
Author(s):  
Qianzhun Huang ◽  
Xiaoyang Su ◽  
Ning Fang ◽  
Jian Huang
Keyword(s):  
Tumor Microenvironment ◽  
Circadian Rhythms ◽  
Lung Adenocarcinoma ◽  
Circadian Clock ◽  
Drug Sensitivity ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Functional Enrichment ◽  
Expression Levels ◽  
Circadian Clock Genes

Abstract Background: Dysregulated circadian dynamic balance is strongly associated with cancer development. However, biological functions of circadian rhythms in lung adenocarcinoma (LUAD) have not been elucidated. This study aimed at valuating the modulatory effects of circadian rhythms in the LUAD tumor microenvironment.Methods: Multiple open-source bioinformatics research platforms are used to comprehensively elucidate the expression level, prognosis, potential biological function, drug sensitivity, and immune microenvironment of circadian clock genes in LUAD.Results: Most circadian clock genes in LUAD are dysregulated and are strongly correlated with patient prognosis, and missense mutations at splicing sites of these genes. Besides, these genes are closely associated with some well-known cancer-related marker pathways, which are mainly involved in the inhibition of the Apoptosis, Cell cycle, and DNA Damage Response Pathway. Furthermore, functional enrichment analysis revealedthat circadian clock genes regulate transcription factor activities and circadian rhythms in LUAD tissues. As for drug sensitivity, high expression of CLOCK, CRY1, and NR1D2 as well as suppressedPER2 and CRY2 expression levels are associated with drug resistance. The expression levels of circadian clock genes in LUAD correlate with immune infiltration and are involved in the regulation of immunosuppression.Conclusions: Our multi-omics analysis provides a more comprehensive understanding of the molecular mechanisms of the circadian clock genes in LUAD and provides new insights for a more precise screening of prognostic biomarkers and immunotherapy.

scholarly journals Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4877 ◽  
Author(s):  
Azka Hassan ◽  
Jamil Ahmad ◽  
Hufsah Ashraf ◽  
Amjad Ali
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Damage Control ◽  
Vital Role ◽  
Biochemical Networks ◽  
Jet Lag ◽  
Peripheral Tissues ◽  
Modeling And Analysis ◽  
Circadian Clock Proteins

Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.

scholarly journals Chronic Corticosterone Disrupts the Circadian Rhythm of CRH Expression and M6a RNA Methylation in the Chicken Hypothalamus

2021 ◽  
Author(s):  
Yang Yang ◽  
Wanwan Han ◽  
Aijia Zhang ◽  
Mindie Zhao ◽  
Wei Cong ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Clock Genes ◽  
Diurnal Fluctuation ◽  
Opposite Pattern ◽  
Rna Methylation ◽  
Diurnal Patterns ◽  
M6a Rna Methylation

Abstract Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m6A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m6A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. Here, we show that chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m6A level oscillates in an opposite pattern to CRH mRNA, with lowest m6A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m6A methylation with significantly increased level at night. Further site-specific m6A analysis on 3’UTR of CRH mRNA indicates that higher m6A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m6A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.

Abstract P160: Non-invasive Method to Assess Human Circadian Rhythms

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Daian Chen ◽  
S Justin Thomas ◽  
David A Calhoun ◽  
David M Pollock ◽  
Jennifer S Pollock
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Salivary Cortisol ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Light Exposure ◽  
Rna Isolation ◽  
Buccal Cells ◽  
Non Invasive ◽  
Salivary Melatonin

Circadian rhythms are controlled by an endogenous time-keeping system oscillating approximately on a 24-h cycle under constant conditions. These rhythms depend on a network of interacting genes and proteins, including transcriptional activators such as CLOCK, NPAS2, and ARNTL (BMAL1), which induce transcription of the clock genes Period ( Per1 , Per2 , and Per3 ) and Cryptochrome ( Cry1 and Cry2 ). Human salivary cortisol and melatonin follow a clear circadian rhythm as well. Disruption of the circadian rhythm and sleep-wake cycles are considered risk factors for a variety of health problems, especially hypertension and other cardiovascular and metabolic diseases. Here we put together practical methods for assessing circadian rhythms in adult subjects conducted by each individual. This method is non-invasive, inexpensive and provides a predictive profile of an individual’s circadian rhythm related to clock-controlled gene expression in buccal cells, salivary cortisol, salivary melatonin, and subject’s activity or sleep. Subjects are instructed on how to obtain buccal cells using swabs (Whatman OmniSwab) from the inside of their cheeks and collect saliva using salivettes (Sarstedt) every 4 hours starting at 6am, for 2 consecutive days. Subjects also wear actigraphy watches (Phillips Respironics) during the 2 days, to record their activity, light exposure and estimates of sleep times. To monitor adherence to correct time point collections, each subject is given an electronic vial called eCAP (Information Mediary Corp) that records the exact time the container is opened to place samples once collected. We demonstrate feasibility to extract up to 150ng/μl of RNA (Ambion RNAqueous-Micro Total RNA Isolation Kit) from buccal cells swabs. Salivary melatonin and cortisol are measured by radioimmunoassay (Buhlmann Lab) with melatonin peak levels ranging from 14 to 23 pg/ml and cortisol peak levels ranging from 10 to 24 ng/ml. We suggest that buccal cell expression of clock-controlled genes, salivary melatonin, salivary cortisol, and actigraphy data are valuable in providing reliable assessment of human circadian rhythm profiles under a variety of conditions.

Sleep Deprivation Induces Neuroinflammation and Depressive-like Behaviors by Impairing the Regulation of Circadian Clock Genes Expression in Rats

2020 ◽  
Author(s):  
Chen Xing ◽  
Yanzhao Zhou ◽  
Huan Xu ◽  
Mengnan Ding ◽  
Yifan Zhang ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Circadian Clock ◽  
Glial Cell ◽  
Hpa Axis ◽  
Calcium Binding ◽  
Cell Activation ◽  
Clock Genes ◽  
Sleep Loss ◽  
Genes Expression ◽  
Circadian Clock Genes

Abstract Background: Sleep loss leads to a spectrum of mood disorders such as anxiety, cognitive dysfunction and motor coordination impairment in many individuals. However, the underlying mechanisms are largely unknown. Methods: In this study, we examined the effects of sleep deprivation (SD) on depression and the mechanism by subjecting rats to a slowly rotating platform for 3 days to mimic the process of sleep loss. Sleep-deprived animals were tested behaviorally for anxiety- and depressive-like behaviors. We further studied the effects of SD on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure the circadian clock genes expression in the hypothalamus, glial cell activation and inflammatory cytokine alterations. Results: Our results indicated that SD for 3 days resulted in anxiety- and depressive-like behaviors. SD exaggerated cortisol response to HPA axis, significantly altered the mRNA profile of circadian clock genes, and induced neuroinflammation by increasing the expression of glial cell markers, including the microglial marker ionized calcium-binding adapter molecule 1 (Iba1) and the astroglial marker glial fibrillary acidic protein (GFAP). The expression of M1 and M2 microglial markers (Arg-1 and CD206, respectively) and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were increased in the brain. Conclusion: These results indicated that SD for 3 days induced anxiety- and depression-like behaviors in rats by impairing the regulation of circadian clock genes and inducing neuroinflammation, ultimately resulting in brain injury.

Sleep deprivation: Effects on circadian rhythms of rat brain neurotransmitter receptors

1981 ◽  
Vol 5 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Anna Wirz-Justice ◽  
Irene Tobler ◽  
Marian S. Kafka ◽  
Dieter Naber ◽  
Paul J. Marangos ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Sleep Deprivation ◽  
Rat Brain ◽  
Neurotransmitter Receptors ◽  
Brain Neurotransmitter

Treatment of Excessive Daytime Sleepiness

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S2) ◽  
pp. 9-11
Author(s):  
Mary B. O'Malley
Keyword(s):  
Sleep Deprivation ◽  
Daytime Sleepiness ◽  
Core Body Temperature ◽  
Objective Measure ◽  
Sleep Hygiene ◽  
The Body ◽  
Vigorous Exercise ◽  
Time In Bed ◽  
Heavy Burden ◽  
Good Sleep

The most common cause of sleepiness is sleep deprivation, which is often due to behaviorally induced sleep limitations. One method of preventing impaired or shortened sleep is to ensure good sleep hygiene. It is important to review with patients the principles of sleep hygiene so that they can rule out causal behaviors that might be relatively simple to correct. Principles of good sleep hygiene include maintaining a regular sleep/wake schedule, exposure to light in the morning hours, avoiding caffeine and nicotine especially 4–6 hours before bedtime, avoiding alcohol and heavy meals before sleep, regular exercise (vigorous exercise should be avoided 3–4 hours before sleep), limiting time in bed to the time spent sleeping, and allowing sufficient time to get comfortable and relaxed prior to sleep. Even if one can fall asleep after drinking alcohol or caffeine, sleep maintenance can be curtailed. Sensitivity to these stimulants is often apparent in the latter half of the night. People often fail to recognize that vigorous aerobic workouts close to bedtime makes it harder to fall asleep. This is because a revved up metabolism heats the body up, and thereby delays the normal cooling of the core body temperature which triggers the onset of sleep.One study assessed the sleep of 259 subjects using the Multiple Sleep Latency Test (MSLT), an objective measure of daytime sleepiness that assesses how quickly someone can fall asleep in conducive conditions. The results indicated that many people in the general population carry a very heavy burden of sleepiness (Slide 1). Many physicians were shown to carry pathological levels of sleepiness because of their heavy call schedules and their foreshortened sleep on nights that they are not on call. The average adult needs 8.2 hours of sleep per night, and not surprisingly many studies have found that the sleepiest adults spent ≤6 hours in bed. What makes matters worse is that insight into the impairments of sleepiness erodes rapidly, but other cognitive and somatic impairments continue to mount with regular chronic under-sleeping. When sleepiness is due to chronic sleep deprivation, treatment often consists of scheduling enough time in bed to allow for an adequate amount of sleep.

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