scholarly journals The Circadian Clock and Viral Infections

2020 ◽  
pp. 074873042096776
Author(s):  
Helene Borrmann ◽  
Jane A McKeating ◽  
Xiaodong Zhuang
Keyword(s):  
Circadian Clock ◽  
Clinical Evidence ◽  
Viral Infections ◽  
Peripheral Tissues ◽  
Antiviral Therapies ◽  
Regulatory Circuits ◽  
Fertile Ground ◽  
Central Clock ◽  
And Behavior ◽  
The Brain

The circadian clock controls several aspects of mammalian physiology and orchestrates the daily oscillations of biological processes and behavior. Our circadian rhythms are driven by an endogenous central clock in the brain that synchronizes with clocks in peripheral tissues, thereby regulating our immune system and the severity of infections. These rhythms affect the pharmacokinetics and efficacy of therapeutic agents and vaccines. The core circadian regulatory circuits and clock-regulated host pathways provide fertile ground to identify novel antiviral therapies. An increased understanding of the role circadian systems play in regulating virus infection and the host response to the virus will inform our clinical management of these diseases. This review provides an overview of the experimental and clinical evidence reporting on the interplay between the circadian clock and viral infections, highlighting the importance of virus-clock research.

scholarly journals The Development and Decay of the Circadian Clock in Drosophila melanogaster

2019 ◽  
Vol 1 (4) ◽  
pp. 489-500
Author(s):  
Jia Zhao ◽  
Guy Warman ◽  
James Cheeseman
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Firefly Luciferase ◽  
Whole Body ◽  
Drosophila Model ◽  
Central Clock ◽  
Development And Aging ◽  
Central Oscillator ◽  
The Brain ◽  
Insight Into

The way in which the circadian clock mechanism develops and decays throughout life is interesting for a number of reasons and may give us insight into the process of aging itself. The Drosophila model has been proven invaluable for the study of the circadian clock and development and aging. Here we review the evidence for how the Drosophila clock develops and changes throughout life, and present a new conceptual model based on the results of our recent work. Firefly luciferase lines faithfully report the output of known clock genes at the central clock level in the brain and peripherally throughout the whole body. Our results show that the clock is functioning in embryogenesis far earlier than previously thought. This central clock in the fly remains robust throughout the life of the animal and only degrades immediately prior to death. However, at the peripheral (non-central oscillator level) the clock shows weakened output as the animal ages, suggesting the possibility of the breakdown in the cohesion of the circadian network.

Development of the Molecular Circadian Clock and Its Light Sensitivity in Drosophila Melanogaster

2019 ◽  
Vol 34 (3) ◽  
pp. 272-282 ◽  
Author(s):  
Jia Zhao ◽  
Guy Robert Warman ◽  
Ralf Stanewsky ◽  
James Frederick Cheeseman
Keyword(s):  
Circadian Clock ◽  
Pupal Stage ◽  
Light Sensitivity ◽  
Embryonic Stage ◽  
Constant Darkness ◽  
Behavioral Experiments ◽  
Peripheral Tissues ◽  
Rhythmic Expression ◽  
Central Clock

The importance of the circadian clock for the control of behavior and physiology is well established but how and when it develops is not fully understood. Here the initial expression pattern of the key clock gene period was recorded in Drosophila from embryos in vivo, using transgenic luciferase reporters. PERIOD expression in the presumptive central-clock dorsal neurons started to oscillate in the embryo in constant darkness. In behavioral experiments, a single 12-h light pulse given during the embryonic stage synchronized adult activity rhythms, implying the early development of entrainment mechanisms. These findings suggest that the central clock is functional already during embryogenesis. In contrast to central brain expression, PERIOD in the peripheral cells or their precursors increased during the embryonic stage and peaked during the pupal stage without showing circadian oscillations. Its rhythmic expression only initiated in the adult. We conclude that cyclic expression of PERIOD in the central-clock neurons starts in the embryo, presumably in the dorsal neurons or their precursors. It is not until shortly after eclosion when cyclic and synchronized expression of PERIOD in peripheral tissues commences throughout the animal.

scholarly journals Light sets the brain’s daily clock by regional quickening and slowing of the molecular clockworks at dawn and dusk

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Suil Kim ◽  
Douglas G McMahon
Keyword(s):  
Neural Network ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Clock Gene ◽  
Ex Vivo ◽  
Period Effects ◽  
Free Running ◽  
And Behavior ◽  
The Brain ◽  
Light Input

How daily clocks in the brain are set by light to local environmental time and encode the seasons is not fully understood. The suprachiasmatic nucleus (SCN) is a central circadian clock in mammals that orchestrates physiology and behavior in tune with daily and seasonal light cycles. Here, we have found that optogenetically simulated light input to explanted mouse SCN changes the waveform of the molecular clockworks from sinusoids in free-running conditions to highly asymmetrical shapes with accelerated synthetic (rising) phases and extended degradative (falling) phases marking clock advances and delays at simulated dawn and dusk. Daily waveform changes arise under ex vivo entrainment to simulated winter and summer photoperiods, and to non-24 hr periods. Ex vivo SCN imaging further suggests that acute waveform shifts are greatest in the ventrolateral SCN, while period effects are greatest in the dorsomedial SCN. Thus, circadian entrainment is encoded by SCN clock gene waveform changes that arise from spatiotemporally distinct intrinsic responses within the SCN neural network.

scholarly journals The circadian clock and metabolic homeostasis: entangled networks

2021 ◽  
Author(s):  
Leonardo Vinícius Monteiro de Assis ◽  
Henrik Oster
Keyword(s):  
Circadian Clock ◽  
Molecular Clock ◽  
Biological Processes ◽  
Brain Areas ◽  
Peripheral Tissues ◽  
Integrative View ◽  
Circadian Organization ◽  
Peripheral Clocks ◽  
Central Clock ◽  
Dependent Processes

AbstractThe circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. The synchrony between the daily challenges imposed by the environment needs to be aligned with biological processes and with the internal circadian clock. In this review, it is provided an in-depth view of the molecular functioning of the circadian molecular clock, how this system is organized, and how central and peripheral clocks communicate with each other. In this sense, we provide an overview of the neuro-hormonal factors controlled by the central clock and how they affect peripheral tissues. We also evaluate signals released by peripheral organs and their effects in the central clock and other brain areas. Additionally, we evaluate a possible communication between peripheral tissues as a novel layer of circadian organization by reviewing recent studies in the literature. In the last section, we analyze how the circadian clock can modulate intracellular and tissue-dependent processes of metabolic organs. Taken altogether, the goal of this review is to provide a systemic and integrative view of the molecular clock function and organization with an emphasis in metabolic tissues.

scholarly journals Oxytocin Signaling Acts as a Marker for Environmental Stressors in Zebrafish

2021 ◽  
Vol 22 (14) ◽  
pp. 7459
Author(s):  
Hsin-Ju Chuang ◽  
Chun-Yung Chang ◽  
Huai-Ping Ho ◽  
Ming-Yi Chou
Keyword(s):  
Stress Responses ◽  
Behavioral Outcomes ◽  
Environmental Stressors ◽  
Adult Zebrafish ◽  
Peripheral Tissues ◽  
Stress Indicator ◽  
Oxytocin Receptors ◽  
And Behavior ◽  
The Brain ◽  
Insight Into

The oxytocin system plays a role in stress responses and behavior modulation. However, the effects of oxytocin signaling on stress adaptation remain unclear. Here, we demonstrated the roles of oxytocin signaling as a biomarker under stress conditions in the peripheral tissues (the gills) and central nervous system (the brain). All the environmental stressors downregulated the expression of oxytocin receptors in the gills, and the alteration of the expression of oxytocin receptors was also found in the brain after the acidic (AC) and high-ammonia (HA) treatments. The number of oxytocin neurons was increased after double-deionized (DI) treatment. By transgenic line, Tg(oxtl:EGFP), we also investigated the projections of oxytocin neurons and found oxytocin axon innervations in various nuclei that might regulate the anxiety levels and aggressiveness of adult zebrafish under different environmental stresses. The oxytocin system integrates physiological responses and behavioral outcomes to ensure environmental adaptation in adult zebrafish. Our study provides insight into oxytocin signaling as a stress indicator upon environmental stressors.

scholarly journals A Catalog of GAL4 Drivers for Labeling and Manipulating Circadian Clock Neurons in Drosophila melanogaster

2019 ◽  
Vol 35 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Manabu Sekiguchi ◽  
Kotaro Inoue ◽  
Tian Yang ◽  
Dong-Gen Luo ◽  
Taishi Yoshii
Keyword(s):  
Drosophila Melanogaster ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Daily Rhythms ◽  
Specific Expression ◽  
Central Clock ◽  
And Behavior

Daily rhythms of physiology, metabolism, and behavior are orchestrated by a central circadian clock. In mice, this clock is coordinated by the suprachiasmatic nucleus, which consists of 20,000 neurons, making it challenging to characterize individual neurons. In Drosophila, the clock is controlled by only 150 clock neurons that distribute across the fly’s brain. Here, we describe a comprehensive set of genetic drivers to facilitate individual characterization of Drosophila clock neurons. We screened GAL4 lines that were obtained from Drosophila stock centers and identified 63 lines that exhibit expression in subsets of central clock neurons. Furthermore, we generated split-GAL4 lines that exhibit specific expression in subsets of clock neurons such as the 2 DN2 neurons and the 6 LPN neurons. Together with existing driver lines, these newly identified ones are versatile tools that will facilitate a better understanding of the Drosophila central circadian clock.

scholarly journals Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

2020 ◽  
Vol 21 (5) ◽  
pp. 1554 ◽  
Author(s):  
Nicola Forte ◽  
Alba Clara Fernández-Rilo ◽  
Letizia Palomba ◽  
Vincenzo Di Marzo ◽  
Luigia Cristino
Keyword(s):  
Intestinal Microbiota ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Hypothalamic Area ◽  
Peripheral Tissues ◽  
Regulatory Circuits ◽  
Bidirectional Communication ◽  
Factor Α ◽  
Fat Diets ◽  
The Brain

The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota–gut–brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the “expanded endocannabinoid (eCB) system” or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.

scholarly journals Chronobiology and Metabolism: Is Ketogenic Diet Able to Influence Circadian Rhythm?

2021 ◽  
Vol 15 ◽  
Author(s):  
Elena Gangitano ◽  
Lucio Gnessi ◽  
Andrea Lenzi ◽  
David Ray
Keyword(s):  
Gene Expression ◽  
Circadian Rhythm ◽  
Circadian Clock ◽  
Ketogenic Diet ◽  
Clock Genes ◽  
The Body ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Peripheral Tissues ◽  
Central Clock

Circadian rhythms underpin most physiological processes, including energy metabolism. The core circadian clock consists of a transcription-translation negative feedback loop, and is synchronized to light-dark cycles by virtue of light input from the retina, to the central clock in the suprachiasmatic nucleus in the hypothalamus. All cells in the body have circadian oscillators which are entrained to the central clock by neural and humoral signals. In addition to light entrainment of the central clock in the brain, it now emerges that other stimuli can drive circadian clock function in peripheral tissues, the major one being food. This can then drive the liver clock to be misaligned with the central brain clock, a situation of internal misalignment with metabolic disease consequences. Such misalignment is prevalent, with shift workers making up 20% of the working population. The effects of diet composition on the clock are not completely clarified yet. High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models. Ketogenic diet (KD) is able to induce a metabolic switch from carbohydrate to fatty acid oxidation, miming a fasting state. In recent years, some animal studies have been conducted to investigate the ability of the KD to modify circadian gene expression, and demonstrated that the KD alters circadian rhythm and induces a rearrangement of metabolic gene expression. These findings may lead to new approaches to obesity and metabolic pathologies treatment.

Review of Self-regulation of the Brain and Behavior.

1985 ◽  
Vol 30 (12) ◽  
pp. 999-999
Author(s):  
Gerald S. Wasserman
Keyword(s):  
Self Regulation ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain
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