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Neurologic Clinics Aug 2019Circadian rhythms are observed in most physiologic functions across a variety of species and are controlled by a master pacemaker in the brain called the suprachiasmatic... (Review)
Review
Circadian rhythms are observed in most physiologic functions across a variety of species and are controlled by a master pacemaker in the brain called the suprachiasmatic nucleus. The complex nature of the circadian system and the impact of circadian disruption on sleep, health, and well-being support the need to assess internal circadian timing in the clinical setting. The ability to assess circadian rhythms and the degree of circadian disruption can help in categorizing subtypes or even new circadian rhythm disorders and aid in the clinical management of the these disorders.
Topics: Biomarkers; Brain; Circadian Rhythm; Humans; Melatonin; Sleep
PubMed: 31256786
DOI: 10.1016/j.ncl.2019.05.001 -
Biochemical Pharmacology Sep 2021Daylight is ubiquitous and is crucial for mammalian vision as well as for non-visual input to the brain via the intrinsically photosensitive retinal ganglion cells... (Review)
Review
Daylight is ubiquitous and is crucial for mammalian vision as well as for non-visual input to the brain via the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin. The ipRGCs project to the circadian clock in the suprachiasmatic nuclei and thereby ensure entrainment to the 24-hour day-night cycle, and changes in daylength trigger the appropriate seasonal behaviours. The ipRGCs also project to the perihabenular nucleus and surrounding brain regions that modulate mood, stress and learning in animals and humans. Given that light has strong direct effects on mood, cognition, alertness, performance, and sleep, light can be considered a "drug" to treat many clinical conditions. Light therapy is already well established for winter and other depressions and circadian sleep disorders. Beyond visual and non-visual effects via the retina, daylight contributes to prevent myopia in the young by its impact on eye development, and is important for Vitamin D synthesis and bone health via the skin. The sun is the most powerful light source and, dependent on dose, its ultraviolet radiance is toxic for living organisms and can be used as a disinfectant. Most research involves laboratory-based electric light, without the dynamic and spectral changes that daylight undergoes moment by moment. There is a gap between the importance of daylight for human beings and the amount of research being done on this subject. Daylight is taken for granted as an environmental factor, to be enjoyed or avoided, according to conditions. More daylight awareness in architecture and urban design beyond aesthetic values and visual comfort may lead to higher quality work and living environments. Although we do not yet have a factual basis for the assumption that natural daylight is overall "better" than electric light, the environmental debate mandates serious consideration of sunlight not just for solar power but also as biologically necessary for sustainable and healthy living.
Topics: Circadian Clocks; Circadian Rhythm; Humans; Light; Mood Disorders; Myopia; Photoperiod; Retina; Retinal Ganglion Cells; Rod Opsins; Suprachiasmatic Nucleus; Vitamin D
PubMed: 33129807
DOI: 10.1016/j.bcp.2020.114304 -
Trends in Neurosciences Jun 2022The circadian clock provides cue-independent anticipatory signals for diurnal rhythms of baseline glucose levels and glucose tolerance. The central circadian clock is... (Review)
Review
The circadian clock provides cue-independent anticipatory signals for diurnal rhythms of baseline glucose levels and glucose tolerance. The central circadian clock is located in the hypothalamic suprachiasmatic nucleus (SCN), which comprises primarily GABAergic neurons. The SCN clock regulates physiological diurnal rhythms of endogenous glucose production (EGP) and hepatic insulin sensitivity through neurohumoral mechanisms. Disruption of the molecular circadian clock is associated with the extended dawn phenomenon (DP) in type 2 diabetes (T2D), referring to hyperglycemia in the early morning without nocturnal hypoglycemia. The DP affects nearly half of patients with diabetes, with poorly defined etiology and a lack of targeted therapy. Here we review neural and secreted factors in physiological diurnal rhythms of glucose metabolism and their pathological implications for the DP.
Topics: Circadian Clocks; Circadian Rhythm; Diabetes Mellitus, Type 2; Glucose; Humans; Hyperglycemia; Suprachiasmatic Nucleus
PubMed: 35466006
DOI: 10.1016/j.tins.2022.03.010 -
Hypertension (Dallas, Tex. : 1979) Nov 2021Accumulating evidence suggests that the molecular circadian clock is crucial in blood pressure (BP) control. Circadian rhythms are controlled by the central clock, which... (Review)
Review
Accumulating evidence suggests that the molecular circadian clock is crucial in blood pressure (BP) control. Circadian rhythms are controlled by the central clock, which resides in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks throughout the body. Both light and food cues entrain these clocks but whether these cues are important for the circadian rhythm of BP is a growing area of interest. The peripheral clocks in the smooth muscle, perivascular adipose tissue, liver, adrenal gland, and kidney have been recently implicated in the regulation of BP rhythm. Dysregulation of the circadian rhythm of BP is associated with adverse cardiorenal outcomes and increased risk of cardiovascular mortality. In this review, we summarize the most recent advances in peripheral clocks as BP regulators, highlight the adverse outcomes of disrupted circadian BP rhythm in hypertension, and provide insight into potential future work in areas exploring the circadian clock in BP control and chronotherapy. A better understanding of peripheral clock function in regulating the circadian rhythm of BP will help pave the way for targeted therapeutics in the treatment of circadian BP dysregulation and hypertension.
Topics: Animals; Antihypertensive Agents; Blood Pressure; CLOCK Proteins; Circadian Clocks; Circadian Rhythm; Clinical Trials as Topic; Gene Expression Regulation; Humans; Hypertension
PubMed: 34601963
DOI: 10.1161/HYPERTENSIONAHA.121.14519 -
Nature Reviews. Endocrinology Oct 2019Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription-translation feedback loops of specific genes, which are referred to as... (Review)
Review
Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription-translation feedback loops of specific genes, which are referred to as 'circadian clock genes'. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. The circadian system regulates virtually all physiological processes, which are further modulated by changes in the external environment, such as light exposure and the timing of food intake. Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep-wake cycles has long-term consequences for our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. Although the hypothalamic-pituitary-thyroid axis is under the control of the circadian clock via the suprachiasmatic nucleus pacemaker, daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. Disruption of circadian rhythms has been recognized as a perturbation of the endocrine system and of cell cycle progression. Expression profiles of circadian clock genes are abnormal in well-differentiated thyroid cancer but not in the benign nodules or a healthy thyroid. Therefore, the characterization of the thyroid clock machinery might improve the preoperative diagnosis of thyroid cancer.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Humans; Jet Lag Syndrome; Thyroid Diseases; Thyroid Gland
PubMed: 31406343
DOI: 10.1038/s41574-019-0237-z -
Experimental and Therapeutic Medicine Mar 2021Sleep is a physiological global state composed of two different phases: Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The control mechanisms of sleep... (Review)
Review
Sleep is a physiological global state composed of two different phases: Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The control mechanisms of sleep manifest at the level of genetic, biological and cellular organization. Several brain areas, including the basal forebrain, thalamus, and hypothalamus, take part in regulating the activity of this status of life. The signals between different brain regions and those from cortical areas to periphery are conducted through various neuromediators, which are known to either promote wakefulness or sleep. Among others, serotonin, norepinephrine, histamine, hypocretin (orexin), acetylcholine, dopamine, glutamate, and gamma-aminobutyric acid are known to orchestrate the intrinsic mechanisms of sleep neurobiology. Several models that explain the transition and the continuity between wakefulness, NREM sleep and REM sleep have been proposed. All of these models include neurotransmitters as ligands in a complex reciprocal connectivity across the key-centers taking part in the regulation of sleep. Moreover, various environmental cues are integrated by a central pacemaker-located in the suprachiasmatic nucleus-which is able to connect with cortical regions and with peripheral tissues in order to promote the sleep-wake pattern.
PubMed: 33603879
DOI: 10.3892/etm.2021.9703 -
Neurologic Clinics Aug 2019Endogenous central and peripheral circadian oscillators are key to organizing multiple aspects of mammalian physiology; this clock tracks the day-night cycle and governs... (Review)
Review
Endogenous central and peripheral circadian oscillators are key to organizing multiple aspects of mammalian physiology; this clock tracks the day-night cycle and governs behavioral and physiologic rhythmicity. Flexibility in the timing and duration of sleep and wakefulness, critical to the survival of species, is the result of a complex, dynamic interaction between 2 regulatory processes: the clock and a homeostatic drive that increases with wake duration and decreases during sleep. When circadian rhythmicity and sleep homeostasis are misaligned-as in shifted schedules, time zone transitions, aging, or disease-sleep, metabolic, and other disorders may ensue.
Topics: Animals; Circadian Rhythm; Homeostasis; Humans; Sleep; Wakefulness
PubMed: 31256784
DOI: 10.1016/j.ncl.2019.03.001 -
Advances in Experimental Medicine and... 2020The basic helix-loop-helix-PAS transcription factor (CLOCK, Circadian locomotor output cycles protein kaput) was discovered in 1994 as a circadian clock. Soon after its... (Review)
Review
The basic helix-loop-helix-PAS transcription factor (CLOCK, Circadian locomotor output cycles protein kaput) was discovered in 1994 as a circadian clock. Soon after its discovery, the circadian clock, Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL, also call BMAL1), was shown to regulate adiposity and body weight by controlling on the brain hypothalamic suprachiasmatic nucleus (SCN). Farther, circadian clock genes were determined to exert several of lipid metabolic and diabetes effects, overall indicating that CLOCK and BMAL1 act as a central master circadian clock. A master circadian clock acts through the neurons and hormones, with expression in the intestine, liver, kidney, lung, heart, SCN of brain, and other various cell types of the organization. Among circadian clock genes, numerous metabolic syndromes are the most important in the regulation of food intake (via regulation of circadian clock genes or clock-controlled genes in peripheral tissue), which lead to a variation in plasma phospholipids and tissue phospholipids. Circadian clock genes affect the regulation of transporters and proteins included in the regulation of phospholipid metabolism. These genes have recently received increasing recognition because a pharmacological target of circadian clock genes may be of therapeutic worth to make better resistance against insulin, diabetes, obesity, metabolism syndrome, atherosclerosis, and brain diseases. In this book chapter, we focus on the regulation of circadian clock and summarize its phospholipid effect as well as discuss the chemical, physiology, and molecular value of circadian clock pathway regulation for the treatment of plasma lipids and atherosclerosis.
Topics: ARNTL Transcription Factors; CLOCK Proteins; Circadian Clocks; Circadian Rhythm; Humans; Lipid Metabolism; Metabolic Diseases; Suprachiasmatic Nucleus
PubMed: 32705594
DOI: 10.1007/978-981-15-6082-8_5 -
Annual Review of Neuroscience Jul 2023This review explores the interface between circadian timekeeping and the regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity... (Review)
Review
This review explores the interface between circadian timekeeping and the regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity across many time domains, their cell-autonomous circadian clocks exert a particular role in controlling longer-term oscillations of brain function: the maintenance of sleep states and the circadian ordering of sleep and wakefulness. This is most evident in the central circadian pacemaker, the suprachiasmatic nucleus, where the molecular clock of astrocytes suffices to drive daily cycles of neuronal activity and behavior. In Alzheimer's disease, sleep impairments accompany cognitive decline. In mouse models of the disease, circadian disturbances accelerate astroglial activation and other brain pathologies, suggesting that daily functions in astrocytes protect neuronal homeostasis. In brain cancer, treatment in the morning has been associated with prolonged survival, and gliomas have daily rhythms in gene expression and drug sensitivity. Thus, circadian time is fast becoming critical to elucidating reciprocal astrocytic-neuronal interactions in health and disease.
Topics: Mice; Animals; Astrocytes; Circadian Rhythm; Circadian Clocks; Sleep; Suprachiasmatic Nucleus
PubMed: 36854316
DOI: 10.1146/annurev-neuro-100322-112249