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Purinergic Signalling Mar 2023Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the... (Review)
Review
Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.
Topics: Circadian Rhythm; Suprachiasmatic Nucleus; Adenosine Triphosphate
PubMed: 35939197
DOI: 10.1007/s11302-022-09881-3 -
Journal of Pineal Research May 2024The circadian timing system controls glucose metabolism in a time-of-day dependent manner. In mammals, the circadian timing system consists of the main central clock in... (Review)
Review
The circadian timing system controls glucose metabolism in a time-of-day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a period of approximately 24-h are generated by the transcriptional-translational feedback loops of a set of core clock genes. Glucose homeostasis is one of the daily rhythms controlled by this circadian timing system. The central pacemaker in the SCN controls glucose homeostasis through its neural projections to hypothalamic hubs that are in control of feeding behavior and energy metabolism. Using hormones such as adrenal glucocorticoids and melatonin and the autonomic nervous system, the SCN modulates critical processes such as glucose production and insulin sensitivity. Peripheral clocks in tissues, such as the liver, muscle, and adipose tissue serve to enhance and sustain these SCN signals. In the optimal situation all these clocks are synchronized and aligned with behavior and the environmental light/dark cycle. A negative impact on glucose metabolism becomes apparent when the internal timing system becomes disturbed, also known as circadian desynchrony or circadian misalignment. Circadian desynchrony may occur at several levels, as the mistiming of light exposure or sleep will especially affect the central clock, whereas mistiming of food intake or physical activity will especially involve the peripheral clocks. In this review, we will summarize the literature investigating the impact of circadian desynchrony on glucose metabolism and how it may result in the development of insulin resistance. In addition, we will discuss potential strategies aimed at reinstating circadian synchrony to improve insulin sensitivity and contribute to the prevention of type 2 diabetes.
Topics: Humans; Animals; Circadian Rhythm; Glucose; Circadian Clocks; Suprachiasmatic Nucleus
PubMed: 38695262
DOI: 10.1111/jpi.12956 -
Advances in Experimental Medicine and... 2021The suprachiasmatic nucleus houses the master clock, but the genes which encode the circadian clock components are also expressed throughout the brain. Here, we review... (Review)
Review
The suprachiasmatic nucleus houses the master clock, but the genes which encode the circadian clock components are also expressed throughout the brain. Here, we review how circadian clock transcription factors regulate neuromodulator systems such as histamine, dopamine, and orexin that promote arousal. These circadian transcription factors all lead to repression of the histamine, dopamine, and orexin systems during the sleep period, so ensuring integration with the ecology of the animal. If these transcription factors are deleted or mutated, in addition to the global disturbances in circadian rhythms, this causes a chronic up-regulation of neuromodulators leading to hyperactivity, elevated mood, and reduced sleep, which have been suggested to be states resembling mania.
Topics: Animals; Brain; Circadian Clocks; Circadian Rhythm; Sleep; Suprachiasmatic Nucleus
PubMed: 34773227
DOI: 10.1007/978-3-030-81147-1_5 -
Advances in Experimental Medicine and... 2022With the earth's 24-h rotation cycle, physiological function fluctuates in both diurnal and nocturnal animals, thereby ensuring optimal functioning of the body. The main... (Review)
Review
With the earth's 24-h rotation cycle, physiological function fluctuates in both diurnal and nocturnal animals, thereby ensuring optimal functioning of the body. The main regulator of circadian rhythm is the suprachiasmatic nucleus (SCN), which is considered the main pacemaker or "central clock" of the body. Located in the anterior hypothalamus, the SCN influences the activity of other brain regions, as well as peripheral organs, through the release of melatonin and corticosteroids. The SCN can be entrained by several cues, with light being the major cue. Light information from the retina is received by the SCN via the retinohypothalamic tract. Non-photic cues such as temperature and exercise can also entrain the SCN, while feeding time can entrain the "molecular clock" contained within peripheral tissues. This enables organs such as the gastrointestinal (GI) tract to coordinate function with environmental factors, such as food availability.The GI tract, which has the main functions of receiving and digesting food, and expelling waste, also shows oscillations in its activity during the circadian cycle. While these changes are evident under normal conditions, GI function is affected when normal circadian rhythm is disrupted. Recent reviews have assessed interactions between the central clock and gut clock; as such, this review aims to focus on the presence of endogenous circadian rhythms in the GI tract, with particular focus to changes to gastrointestinal motility.
Topics: Animals; Suprachiasmatic Nucleus; Circadian Rhythm; Melatonin; Food; Gastrointestinal Motility
PubMed: 36587158
DOI: 10.1007/978-3-031-05843-1_18 -
Nature Metabolism Jun 2024The daily light-dark cycle is a key zeitgeber (time cue) for entraining an organism's biological clock, whereby light sensing by retinal photoreceptors, particularly... (Review)
Review
The daily light-dark cycle is a key zeitgeber (time cue) for entraining an organism's biological clock, whereby light sensing by retinal photoreceptors, particularly intrinsically photosensitive retinal ganglion cells, stimulates the suprachiasmatic nucleus of the hypothalamus, a central pacemaker that in turn orchestrates the rhythm of peripheral metabolic activities. Non-rhythmic effects of light on metabolism have also been long known, and their transduction mechanisms are only beginning to unfold. Here, we summarize emerging evidence that, in mammals, light exposure or deprivation profoundly affects glucose homeostasis, thermogenesis and other metabolic activities in a clock-independent manner. Such light regulation could involve melanopsin-based, intrinsically photosensitive retinal ganglion cell-initiated brain circuits via the suprachiasmatic nucleus of the hypothalamus and other nuclei, or direct stimulation of opsins expressed in the hypothalamus, adipose tissue, blood vessels and skin to regulate sympathetic tone, lipolysis, glucose uptake, mitochondrial activation, thermogenesis, food intake, blood pressure and melanogenesis. These photic signalling events may coordinate with circadian-based mechanisms to maintain metabolic homeostasis, with dysregulation of this system underlying metabolic diseases caused by aberrant light exposure, such as environmental night light and shift work.
Topics: Animals; Circadian Rhythm; Light; Humans; Mammals; Suprachiasmatic Nucleus; Homeostasis; Thermogenesis; Glucose; Photoperiod; Rod Opsins
PubMed: 38831000
DOI: 10.1038/s42255-024-01051-6 -
Obesity (Silver Spring, Md.) Jul 2020In mammals, time and metabolism are tightly coupled variables; this relationship can be illustrated by numerous examples, such as the circadian variation in food intake... (Review)
Review
In mammals, time and metabolism are tightly coupled variables; this relationship can be illustrated by numerous examples, such as the circadian variation in food intake or the circadian response to a glucose bolus. We review evidence that the interaction between the suprachiasmatic nucleus and the arcuate nucleus plays a key role in the execution of these functions. The nuclei are reciprocally connected via different projections, and this interaction provides an ideal anatomical framework to modify the temporal output of the hypothalamus to metabolic organs as a consequence of the feedback from the periphery. The suprachiasmatic nucleus-arcuate nucleus relationship is essential to integrate metabolic information into the circadian system and thus adapt circadian rhythms in core body temperature, locomotor activity, food intake, and circulating molecules such as glucose and corticosterone. With the rise in obesity-associated diseases in the world population, gaining knowledge about this relationship, and the consequences of disturbing this liaison, is essential to understand the pathogenesis of obesity.
Topics: Arcuate Nucleus of Hypothalamus; Circadian Rhythm; Female; Humans; Male; Suprachiasmatic Nucleus
PubMed: 32538539
DOI: 10.1002/oby.22774 -
International Journal of Environmental... Dec 2022The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and... (Review)
Review
The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and responds to several inputs, including food intake, light/dark cycle, sleep/wake cycle, and physical activity. The circadian timing system comprises a central clock located in the suprachiasmatic nucleus (SCN) and tissue-specific clocks in peripheral tissues. Several studies show that the desynchronization of central and peripheral clocks is associated with an increased incidence of insulin resistance (IR) and related diseases. In this review, we discuss the current knowledge of molecular and cellular mechanisms underlying the impact of circadian clock dysregulation on insulin action. We focus our attention on two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family (PHLPP) family and the deacetylase Sirtuin1. We believe that literature data, herein summarized, suggest that a thorough change of life habits, with the return to synchronized food intake, physical activity, and rest, would doubtless halt the vicious cycle linking IR to dysregulated circadian rhythms. However, since such a comprehensive change may be incompatible with the demand of modern society, clarifying the pathways involved may, nonetheless, contribute to the identification of therapeutic targets that may be exploited to cure or prevent IR-related diseases.
Topics: Humans; Circadian Clocks; Insulin Resistance; Circadian Rhythm; Suprachiasmatic Nucleus; Photoperiod
PubMed: 36612350
DOI: 10.3390/ijerph20010029 -
Reproduction (Cambridge, England) Feb 2023In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of...
IN BRIEF
In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of communication between the suprachiasmatic nucleus and the ovaries where such neural information determines ovulation.
ABSTRACT
The suprachiasmatic nucleus (SCN) regulates the activity of several peripheral organs through a parasympathetic-sympathetic pathway. Previously, we demonstrated that atropine (ATR) microinjection in the right SCN of rats during proestrus blocks ovulation. In the present study, we analysed whether the vagus nerve is one of the neural pathways by which the SCN regulates ovulation. For this, CIIZ-V strain cyclic rats on the day of proestrus were microinjected with a saline solution (vehicle) or ATR in the right or left SCN, which was followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. Some animal groups were sacrificed (i) on the same day of the surgery to measure oestradiol, progesterone and luteinizing hormone (LH) levels or (ii) at 24 h after surgery to evaluate ovulation. The left vagotomy in rats microinjected with ATR in the left SCN did not modify ovulation. In rats with ATR microinjection in the right SCN, the right vagotomy increased the levels of steroids and LH on the proestrus and ovulatory response. The present results suggest that the right vagus nerve plays a role in the multisynaptic pathways of communication between the SCN and the ovaries and indicate that such neural information participates in the regulation of the oestradiol and progesterone surge, which triggers the preovulatory peak of LH and determines ovulation.
Topics: Female; Rats; Animals; Progesterone; Luteinizing Hormone; Suprachiasmatic Nucleus; Ovulation; Estradiol; Atropine; Vagus Nerve
PubMed: 36342662
DOI: 10.1530/REP-22-0119 -
Neuroscience and Biobehavioral Reviews Aug 2021The master clock, suprachiasmatic nucleus, is believed to control peripheral circadian oscillators throughout the brain and body. However, recent data suggest there is a... (Review)
Review
The master clock, suprachiasmatic nucleus, is believed to control peripheral circadian oscillators throughout the brain and body. However, recent data suggest there is a circadian clock involved in learning and memory, potentially housed in the hippocampus, which is capable of acting independently of the master clock. Curiously, the hippocampal clock appears to be influenced by the master clock and by hippocampal dependent learning, while under certain conditions it may also revert to its endogenous circadian rhythm. Here we propose a mechanism by which the hippocampal clock could locally determine the nature of its entrainment. We introduce a novel theoretical framework, inspired by but extending beyond the hippocampal memory clock, which provides a new perspective on how circadian clocks throughout the brain coordinate their rhythms. Importantly, a local clock for memory would suggest that hippocampal-dependent learning at the same time every day should improve memory, opening up a range of possibilities for non-invasive therapies to alleviate the detrimental effects of circadian rhythm disruption on human health.
Topics: Brain; Circadian Clocks; Circadian Rhythm; Humans; Learning; Suprachiasmatic Nucleus
PubMed: 33476672
DOI: 10.1016/j.neubiorev.2020.11.032 -
The Canadian Journal of Cardiology Dec 2023Circadian rhythms are crucial for maintaining vascular function and disruption of these rhythms are associated with negative health outcomes including cardiovascular... (Review)
Review
Circadian rhythms are crucial for maintaining vascular function and disruption of these rhythms are associated with negative health outcomes including cardiovascular disease and hypertension. Circadian rhythms are regulated by the central clock within the suprachiasmatic nucleus of the hypothalamus and peripheral clocks located in nearly every cell type in the body, including cells within the heart and vasculature. In this review, we summarize the most recent preclinical and clinical research linking circadian disruption, with a focus on molecular circadian clock mechanisms, in atherosclerosis and hypertension. Furthermore, we provide insight into potential future chronotherapeutics for hypertension and vascular disease. A better understanding of the influence of daily rhythms in behaviour, such as sleep/wake cycles, feeding, and physical activity, as well as the endogenous circadian system on cardiovascular risk will help pave the way for targeted approaches in atherosclerosis and hypertension treatment/prevention.
Topics: Humans; Circadian Rhythm; Circadian Clocks; Suprachiasmatic Nucleus; Hypertension; Atherosclerosis
PubMed: 37355229
DOI: 10.1016/j.cjca.2023.06.416