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International Journal of Molecular... Feb 2023Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social... (Review)
Review
Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h. Circadian rhythms govern the temporal features of physiology and behavior, and are set to precisely 24 h primarily by exposure to light during the solar day, though other factors, such as the timing of meals, can also affect circadian rhythms. Circadian rhythms are significantly affected by night shift work because of exposure to nocturnal light, electronic devices, and shifts in the timing of meals. Night shift workers are at increased risk for metabolic disorder, as well as several types of cancer. Others who are exposed to artificial light at night or late mealtimes also show disrupted circadian rhythms and increased metabolic and cardiac disorders. It is imperative to understand how disrupted circadian rhythms alter metabolic function to develop strategies to mitigate their negative effects. In this review, we provide an introduction to circadian rhythms, physiological regulation of homeostasis by the suprachiasmatic nucleus (SCN), and SCN-mediated hormones that display circadian rhythms, including melatonin and glucocorticoids. Next, we discuss circadian-gated physiological processes including sleep and food intake, followed by types of disrupted circadian rhythms and how modern lighting disrupts molecular clock rhythms. Lastly, we identify how disruptions to hormones and metabolism can increase susceptibility to metabolic syndrome and risk for cardiovascular diseases, and discuss various strategies to mitigate the harmful consequences associated with disrupted circadian rhythms on human health.
Topics: Humans; Circadian Rhythm; Suprachiasmatic Nucleus; Sleep; Melatonin; Eating; Circadian Clocks; Light
PubMed: 36834801
DOI: 10.3390/ijms24043392 -
Seminars in Cell & Developmental Biology Jun 2022Circadian rhythms are ~24 h cycles of behavior and physiology that are generated by a network of molecular clocks located in nearly every tissue in the body. In... (Review)
Review
Circadian rhythms are ~24 h cycles of behavior and physiology that are generated by a network of molecular clocks located in nearly every tissue in the body. In mammals, the circadian system is organized hierarchically such that the suprachiasmatic nucleus (SCN) is the main circadian clock that receives light information from the eye and entrains to the light-dark cycle. The SCN then coordinates the timing of tissue clocks so internal rhythms are aligned with environmental cycles. Estrogens interact with the circadian system to regulate biological processes. At the molecular level, estrogens and circadian genes interact to regulate gene expression and cell biology. Estrogens also regulate circadian behavior across the estrous cycle. The timing of ovulation during the estrous cycle requires coincident estrogen and SCN signals. Studies using circadian gene reporter mice have also elucidated estrogen regulation of peripheral tissue clocks and metabolic rhythms. This review synthesizes current understanding of the interplay between estrogens and the circadian system, with a focus on female rodents, in regulating molecular, physiological, and behavioral processes.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Estrogens; Female; Mammals; Mice; Photoperiod; Suprachiasmatic Nucleus
PubMed: 33975754
DOI: 10.1016/j.semcdb.2021.04.010 -
Molecules (Basel, Switzerland) Nov 2022Melatonin, -acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly... (Review)
Review
Melatonin, -acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina's exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin's role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.
Topics: Melatonin; Pineal Gland; Nerve Growth Factors; Suprachiasmatic Nucleus; Sleep; Transforming Growth Factor beta
PubMed: 36431847
DOI: 10.3390/molecules27227742 -
Journal of Huntington's Disease 2023Our physiology and behavior follow precise daily programs that adapt us to the alternating opportunities and challenges of day and night. Under experimental isolation,... (Review)
Review
Our physiology and behavior follow precise daily programs that adapt us to the alternating opportunities and challenges of day and night. Under experimental isolation, these rhythms persist with a period of approximately one day (circadian), demonstrating their control by an internal autonomous clock. Circadian time is created at the cellular level by a transcriptional/translational feedback loop (TTFL) in which the protein products of the Period and Cryptochrome genes inhibit their own transcription. Because the accumulation of protein is slow and delayed, the system oscillates spontaneously with a period of ∼24 hours. This cell-autonomous TTFL controls cycles of gene expression in all major tissues and these cycles underpin our daily metabolic programs. In turn, our innumerable cellular clocks are coordinated by a central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. When isolated in slice culture, the SCN TTFL and its dependent cycles of neural activity persist indefinitely, operating as "a clock in a dish". In vivo, SCN time is synchronized to solar time by direct innervation from specialized retinal photoreceptors. In turn, the precise circadian cycle of action potential firing signals SCN-generated time to hypothalamic and brain stem targets, which co-ordinate downstream autonomic, endocrine, and behavioral (feeding) cues to synchronize and sustain the distributed cellular clock network. Circadian time therefore pervades every level of biological organization, from molecules to society. Understanding its mechanisms offers important opportunities to mitigate the consequences of circadian disruption, so prevalent in modern societies, that arise from shiftwork, aging, and neurodegenerative diseases, not least Huntington's disease.
Topics: Animals; Circadian Rhythm; Huntington Disease; Suprachiasmatic Nucleus; Gene Expression Regulation; Mammals
PubMed: 37125558
DOI: 10.3233/JHD-230571 -
Handbook of Clinical Neurology 2021Melanopsin retinal ganglion cells (mRGCs) are the third class of retinal photoreceptors with unique anatomical, electrophysiological, and biological features. There are... (Review)
Review
Melanopsin retinal ganglion cells (mRGCs) are the third class of retinal photoreceptors with unique anatomical, electrophysiological, and biological features. There are different mRGC subtypes with differential projections to the brain. These cells contribute to many nonimage-forming functions of the eye, the most relevant being the photoentrainment of circadian rhythms through the projections to the suprachiasmatic nucleus of the hypothalamus. Other relevant biological functions include the regulation of the pupillary light reflex, mood, alertness, and sleep, as well as a possible role in formed vision. The relevance of the mRGC-related pathways in the brain is highlighted by the role that the dysfunction and/or loss of these cells may play in affecting circadian rhythms and sleep in many neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease and in aging. Moreover, the occurrence of circadian dysfunction is a known risk factor for dementia. In this chapter, the anatomy, physiology, and functions of these cells as well as their resistance to neurodegeneration in mitochondrial optic neuropathies or their predilection to be lost in other neurodegenerative disorders will be discussed.
Topics: Circadian Rhythm; Humans; Retina; Retinal Ganglion Cells; Rod Opsins; Suprachiasmatic Nucleus
PubMed: 34225972
DOI: 10.1016/B978-0-12-819975-6.00020-0 -
Sleep Medicine Clinics Jun 2022In this review, we provide a summary of the field of mammalian circadian neurobiology circa 2015. While many additional details have emerged in the intervening 7 years,... (Review)
Review
In this review, we provide a summary of the field of mammalian circadian neurobiology circa 2015. While many additional details have emerged in the intervening 7 years, understanding of the fundamental structure and function of this critical neural system remains intact. Thus, the present review continues to provide a valuable introduction for those seeking an integrative multilevel overview of the circadian system. In brief, the circadian system comprises a coupled network of molecular/cellular- and tissue-level oscillators, hierarchically coordinated by the hypothalamic suprachiasmatic nuclear circadian pacemaker, and entrained by both photic and nonphotic signals.
Topics: Animals; Circadian Rhythm; Humans; Mammals; Suprachiasmatic Nucleus
PubMed: 35659069
DOI: 10.1016/j.jsmc.2022.02.006 -
The European Journal of Neuroscience Jan 2020In mammals, the central pacemaker that coordinates 24-hr rhythms is located in the suprachiasmatic nucleus (SCN). Individual neurons of the SCN have a molecular basis... (Review)
Review
In mammals, the central pacemaker that coordinates 24-hr rhythms is located in the suprachiasmatic nucleus (SCN). Individual neurons of the SCN have a molecular basis for rhythm generation and hence, they function as cell autonomous oscillators. Communication and synchronization among these neurons are crucial for obtaining a coherent rhythm at the population level, that can serve as a pace making signal for brain and body. Hence, the ability of single SCN neurons to produce circadian rhythms is equally important as the ability of these neurons to synchronize one another, to obtain a bona fide pacemaker at the SCN tissue level. In this chapter we will discuss the mechanisms underlying synchronization, and plasticity herein, which allows adaptation to changes in day length. Furthermore, we will discuss deterioration in synchronization among SCN neurons in aging, and gain in synchronization by voluntary physical activity or exercise.
Topics: Animals; Brain; Circadian Rhythm; Humans; Neurons; Pacemaker, Artificial; Suprachiasmatic Nucleus
PubMed: 30793396
DOI: 10.1111/ejn.14388 -
Science (New York, N.Y.) Feb 2021Circadian clocks temporally coordinate physiology and align it with geophysical time, which enables diverse life-forms to anticipate daily environmental cycles. In... (Review)
Review
Circadian clocks temporally coordinate physiology and align it with geophysical time, which enables diverse life-forms to anticipate daily environmental cycles. In complex organisms, clock function originates from the molecular oscillator within each cell and builds upward anatomically into an organism-wide system. Recent advances have transformed our understanding of how clocks are connected to achieve coherence across tissues. Circadian misalignment, often imposed in modern society, disrupts coordination among clocks and has been linked to diseases ranging from metabolic syndrome to cancer. Thus, uncovering the physiological circuits whereby biological clocks achieve coherence will inform on both challenges and opportunities in human health.
Topics: Animals; Astrocytes; Brain; Cell Communication; Circadian Clocks; Circadian Rhythm; Cues; Feedback, Physiological; Gene Expression Regulation; Homeostasis; Humans; Suprachiasmatic Nucleus Neurons
PubMed: 33574181
DOI: 10.1126/science.abd0951 -
Nature Neuroscience Jan 2024Food intake follows a predictable daily pattern and synchronizes metabolic rhythms. Neurons expressing agouti-related protein (AgRP) read out physiological energetic...
Food intake follows a predictable daily pattern and synchronizes metabolic rhythms. Neurons expressing agouti-related protein (AgRP) read out physiological energetic state and elicit feeding, but the regulation of these neurons across daily timescales is poorly understood. Using a combination of neuron dynamics measurements and timed optogenetic activation in mice, we show that daily AgRP-neuron activity was not fully consistent with existing models of homeostatic regulation. Instead of operating as a 'deprivation counter', AgRP-neuron activity primarily followed the circadian rest-activity cycle through a process that required an intact suprachiasmatic nucleus and synchronization by light. Imposing novel feeding patterns through time-restricted food access or periodic AgRP-neuron stimulation was sufficient to resynchronize the daily AgRP-neuron activity rhythm and drive anticipatory-like behavior through a process that required DMH neurons. These results indicate that AgRP neurons integrate time-of-day information of past feeding experience with current metabolic needs to predict circadian feeding time.
Topics: Animals; Mice; Agouti-Related Protein; Feeding Behavior; Neurons; Suprachiasmatic Nucleus
PubMed: 37957320
DOI: 10.1038/s41593-023-01482-6 -
Handbook of Clinical Neurology 2021For the majority of hypertensive patients, the etiology of their disease is unknown. The hypothalamus is a central structure of the brain which provides an adaptive,... (Review)
Review
For the majority of hypertensive patients, the etiology of their disease is unknown. The hypothalamus is a central structure of the brain which provides an adaptive, integrative, autonomic, and neuroendocrine response to any fluctuations in physiological conditions of the external or internal environment. Hypothalamic insufficiency leads to severe metabolic and functional disorders, including persistent increase in blood pressure. Here, we discuss alterations in the neurochemical organization of the paraventricular and suprachiasmatic nucleus in the hypothalamus of patients who suffered from essential hypertension and died suddenly due to acute coronary failure. The changes observed are hypothesized to contribute to the pathogenesis of disease.
Topics: Corticotropin-Releasing Hormone; Humans; Hypertension; Hypothalamus; Paraventricular Hypothalamic Nucleus; Suprachiasmatic Nucleus
PubMed: 34266604
DOI: 10.1016/B978-0-12-819973-2.00023-X