Regulation And Synchronization Of The Master Circadian Clock By Purinergic Signaling From Suprachiasmatic Nucleus Astrocytes
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Regulation And Synchronization Of The Master Circadian Clock By Purinergic Signaling From Suprachiasmatic Nucleus Astrocytes
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Author : Alisa Diane Womac
language : en
Publisher:
Release Date : 2012
Regulation And Synchronization Of The Master Circadian Clock By Purinergic Signaling From Suprachiasmatic Nucleus Astrocytes written by Alisa Diane Womac and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Molecular, cellular, and physiological processes within an organism are set to occur at specific times throughout the day. The timing of these processes is under control of a biological clock. Nearly all organisms on Earth have biological clocks, ranging from unicellular bacteria and fungi to multicellular plants, insects, reptiles, fish, birds, and mammals. The biological clock is an endogenous time-keeping mechanism that generates the onset of many processes and coordinates the phases of processes over 24 hours. While the biological clock allows these organisms to maintain roughly 24-hour, or circadian, timing in daily processes, many organisms have the ability to set their clocks, or entrain them, to changes in light. In mammals, the suprachiasmatic nucleus (SCN) is the master biological clock that entrains daily physiological and behavioral rhythms to the appropriate times of day and night. The SCN is located in the hypothalamus and contains thousands of neurons and glia that function in coordinating system-level physiological rhythms that are entrained to environmental light cues. Many of these neurons and glia are individual circadian oscillators, and the cellular mechanisms that couple them into ensemble oscillations are emerging. Adenosine triphosphate (ATP) is a transmitter involved in local communication among astrocytes and between astrocytes and neurons. ATP released from astrocytes may play a role in SCN cellular communication and synchrony. Extracellular ATP accumulated rhythmically in the rat SCN in vivo, and ATP released from rat SCN astrocytes in vitro was rhythmic, with a periodicity near 24 hours. ATP released from mouse SCN astrocytes was circadian, and disruption of the molecular clock abolished rhythmic extracellular ATP accumulation. SCN astrocyte cultures with disrupted molecular clocks also had marked reductions in total ATP accumulation compared to SCN astrocyte cultures with functional biological clocks. Furthermore, ATP-induced calcium transients were rhythmic, and this rhythmic purinergic sensitivity was abolished in clock mutant astrocytes. Pharmacological blockade of purinergic signaling, with antagonists of both the P2X7 and P2Y1 receptors, led to a gradual reduction in the amplitude of coordinated ATP accumulation over three days. These purinergic receptor antagonists, as expected, led to a reduction in calcium responses of SCN astrocytes to ATP and led to a dampening of clock gene expression rhythms as determined by PER2::LUC bioluminescence reporting in SCN astrocytes. These data demonstrate that astrocytes of the mammalian SCN rhythmically release ATP and are rhythmically sensitive to ATP in a manner dependent on their intrinsic molecular clock. Ensemble rhythmicity of SCN astrocytes is, in turn, dependent on that rhythmic purinergic signaling via both P2X and P2Y classes of ATP receptors. These results are indicative of a functional role for ATP accumulation within the SCN, with astrocytes releasing ATP every 24 hours for continual signaling onto astrocytes and neurons to maintain daily coordinated synchrony of the clocks in these cells.
Cellular Signaling Events Serving At The Interface Of Cognition Stress And Circadian Clock Entrainment
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Author : Sydney E. Aten
language : en
Publisher:
Release Date : 2021
Cellular Signaling Events Serving At The Interface Of Cognition Stress And Circadian Clock Entrainment written by Sydney E. Aten and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with Astrocytes categories.
Cellular signaling events are integral processes that govern the activity of cells throughout the body and help coordinate key physiological and behavioral processes within organisms. Indeed, the capacity for cells to relay external signals and convert those signals into information that leads to the actuation of signal transduction pathways/induction of genes that mediate a variety of behavioral responses, is crucial to the maintenance of homeostasis within an organism. Such signaling events serve at the interface of complex processes such as circadian clock timing, in addition to cognition and stress—topics that are covered in this dissertation. The suprachiasmatic nucleus (SCN) of the hypothalamus serves as the master circadian timekeeper within the brain. This pacemaker allows for the maintenance of circadian rhythms—endogenous 24-hour oscillations found in nearly every system within the body which enables organisms to adapt to external light timing cues. Notably, in the SCN (and in ancillary brain regions that also express core circadian clock genes), several signaling pathways are involved in the modulation of the transcriptional translational feedback loop (TTFL)—an auto-regulatory model wherein circadian clock genes are negatively regulated by their protein products. One of these pathways is the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) cellular signaling cascade—a pathway that is central to the light entrainment process, which also serves as a link to higher functions such as cognition and mood. In this dissertation, I utilize a host of knockout and transgenic mouse models to expand upon and discuss how the ERK/MAPK pathway and downstream transcription factors such as CREB (cAMP response element-binding protein) and CREB-regulated small, non-coding microRNAs affect circadian clock timing, cognition, and mood. I first present evidence that SynGAP-- a GTPase‐activating protein that serves as a negative regulator of Ras/ERK signaling—is expressed in the SCN and regulates circadian-gated locomotor activity and light entrainment capacity. I also show that individuals with Syngap1 gene mutations have alterations in sleep—a circadian-gated process (Chapter 2). I then demonstrate how circadian clock timing can influence learning and memory. Along these lines, I show that the CREB-regulated microRNA-132 oscillates within the hippocampus (a region known to underlie cognition) and how the dysregulation of the microRNA-132/212 locus alters circadian-gated cognitive capacity (Chapter 3). Furthermore, I show that the miR-132/212 locus is induced by stress and that its dysregulation also influences anxiety-related behaviors (Chapter 4). Given that dysregulation of circadian timing is widely recognized as a core feature of individuals with Major Depressive Disorder, I then expand upon the current understanding of the cellular-level relationship between clock dysregulation and depressive-like behaviors by profiling circadian clock timekeeping capacity after an Unpredictable Chronic Mild Stress (UCMS) paradigm (Chapter 5). Using the same UCMS (mouse model of depression), I also show how a type of non-neuronal cell within the brain—astrocytes—are affected by this chronic stress protocol. Along these lines, I provide evidence that anatomical and functional impairments are observed in the astrocyte syncytial network—which is established within the brain via gap junction coupling (Chapter 6). Finally, I use serial blockface scanning electron microscopy (SBF-SEM) to examine the ultrastructure of astrocyte-neurite contacts within the murine hippocampus (Chapter 7). Taken together, these results provide further support for the role(s) of the ERK/MAPK pathway and CREB-dependent microRNA-132 in circadian clock entrainment, cognition, and stress. They also provide novel insights regarding how chronic stress can lead to perturbations in astrocyte morphology and astrocytic gap junction coupling, and the ultrastructural studies raise interesting questions about astrocyte-neurite interactions within the brain.
Erk Mapk Signaling And The Regulation Of Light Evoked Entrainment Of The Circadian Clock In The Suprachiasmatic Nucleus
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Author : Hyojung Yoon (Molecular biologist)
language : en
Publisher:
Release Date : 2021
Erk Mapk Signaling And The Regulation Of Light Evoked Entrainment Of The Circadian Clock In The Suprachiasmatic Nucleus written by Hyojung Yoon (Molecular biologist) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with Circadian rhythms categories.
Circadian rhythms are generated from the cellular level and synchronized throughout the body. The synchronization of circadian rhythms is mediated by the Suprachiasmatic Nucleus (SCN) in the hypothalamus of the brain, and the SCN is often referred to as a 'master clock' due to its ability to orchestrate the circadian rhythms with peripheral clocks in other organs/tissues/cells of the body. In addition, the SCN also plays a vital role in regulating the adjustment of rhythmicity in response to the external stimulus. Entrainment, the process of adjustment, is regulated by multiple signaling pathways, and among them, ERK signaling pathways are one of the most important ones. This work focused on the regulatory mechanisms of ERK signaling in the SCN. Previously, it has been shown that ERK is involved in the light-dependent regulation of entrainment of the SCN. Details of the regulatory processes of the ERK in the SCN remain unclear. The first part of my dissertation delved into the differential activation of the ERK throughout the day in the SCN. I demonstrated that there is a different spatiotemporal regulation in ERK activation throughout the day. In the second part, the PEA-15 was selected to study ERK regulation in the SCN since PEA-15 is known to regulate the subcellular location of ERK. I characterize the circadian phenotype of the PEA-15 knockout (PEA-15 KO) mice. PEA-15 KO mice displayed distinctive phenotype in ERK expression, inducibility of ERK, and locomotor activity in circadian perspective. The last part of my thesis focused on the cytoplasmic substrate of the ERK – RSK, and the expression of RSK and the kinase activities were profiled in the SCN as well as its role in circadian rhythms. I found that the RSK inhibition attenuated the amplitude of the phase shift without the changes in CREB activation. Together, the complex and inter-related ERK regulation was studied in the SCN from a circadian perspective. It describes the different spatiotemporal regulation of ERK throughout the day and the role of PEA-15 in those processes, as well as the functional role of the RSK as a cytoplasmic substrate of ERK. This work provides insights on unknown territories of cytoplasmic ERK regulation in the SCN and could contribute further to understanding circadian physiology.
Sleep Wake Neurobiology And Pharmacology
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Author : Hans-Peter Landolt
language : en
Publisher: Springer Nature
Release Date : 2019-09-03
Sleep Wake Neurobiology And Pharmacology written by Hans-Peter Landolt and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-09-03 with Medical categories.
This volume connects current ideas and concepts about sleep functions and circadian rhythms with the search for novel target-selective sleep-wake therapeutics. To do so, it provides a timely, state-of-the-art overview of sleep-wake mechanisms in health and disease, ongoing developments in drug discovery, and their prospects for the clinical treatment of sleep-disordered patients. It particularly focuses on the concept that sleep and wakefulness mutually affect each other, and the future therapeutic interventions with either sleep- or wake-promoting agents that are expected to not only improve the quality of sleep but also the waking behavior, cognition, mood and other sleep-associated physiological functions. The chapter 'Sleep Physiology, Circadian Rhythms, Waking Performance and the Development of Sleep-Wake Therapeutics' available open access under a CC BY 4.0 license at link.springer.com
Neuroscience In The 21st Century
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Author : Donald W. Pfaff
language : en
Publisher: Springer
Release Date : 2016-10-27
Neuroscience In The 21st Century written by Donald W. Pfaff and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-10-27 with Medical categories.
Edited and authored by a wealth of international experts in neuroscience and related disciplines, this key new resource aims to offer medical students and graduate researchers around the world a comprehensive introduction and overview of modern neuroscience. Neuroscience research is certain to prove a vital element in combating mental illness in its various incarnations, a strategic battleground in the future of medicine, as the prevalence of mental disorders is becoming better understood each year. Hundreds of millions of people worldwide are affected by mental, behavioral, neurological and substance use disorders. The World Health Organization estimated in 2002 that 154 million people globally suffer from depression and 25 million people from schizophrenia; 91 million people are affected by alcohol use disorders and 15 million by drug use disorders. A more recent WHO report shows that 50 million people suffer from epilepsy and 24 million from Alzheimer’s and other dementias. Because neuroscience takes the etiology of disease—the complex interplay between biological, psychological, and sociocultural factors—as its object of inquiry, it is increasingly valuable in understanding an array of medical conditions. A recent report by the United States’ Surgeon General cites several such diseases: schizophrenia, bipolar disorder, early-onset depression, autism, attention deficit/ hyperactivity disorder, anorexia nervosa, and panic disorder, among many others. Not only is this volume a boon to those wishing to understand the future of neuroscience, it also aims to encourage the initiation of neuroscience programs in developing countries, featuring as it does an appendix full of advice on how to develop such programs. With broad coverage of both basic science and clinical issues, comprising around 150 chapters from a diversity of international authors and including complementary video components, Neuroscience in the 21st Century in its second edition serves as a comprehensive resource to students and researchers alike.
Histamine In The Brain
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Author : Jian-Sheng Lin
language : en
Publisher: Frontiers Media SA
Release Date : 2015-03-18
Histamine In The Brain written by Jian-Sheng Lin and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-03-18 with Brain categories.
Brain aminergic pathways are organized in parallel and interacting systems, which support a range of functions, from homoeostatic regulations to cognitive, and motivational processes. Despite overlapping functional influences, dopamine, serotonin, noradrenaline and histamine systems provide different contributions to these processes. The histaminergic system, long ignored as a major regulator of the sleep-wake cycle, has now been fully acknowledged also as a major coordinator of attention, learning and memory, decision making. Although histaminergic neurons project widely to the whole brain, they are functionally heterogeneous, a feature which may provide the substrate for differential regulation, in a region-specific manner, of other neurotransmitter systems. Neurochemical preclinical studies have clearly shown that histamine interacts and modulates the release of neurotransmitters that are recognized as major modulators of cognitive processing and motivated behaviours. As a consequence, the histamine system has been proposed as a therapeutic target to treat sleep-wake disorders and cognitive dysfunctions that accompany neurodegenerative and neuroinflammatory pathologies. Last decades have witnessed an unexpected explosion of interest in brain histamine system, as new receptors have been discovered and selective ligands synthesised. Nevertheless, the complete picture of the histamine systems fine-tuning and its orchestration with other pathways remains rather elusive. This Research Topic is intended to offer an inter-disciplinary forum that will improve our current understanding of the role of brain histamine and provide the fundamentals necessary to drive innovation in clinical practice and to improve the management and treatment of neurological disorders.
Autonomic Nervous System
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Author : Daniel Pedro Cardinali
language : en
Publisher: Springer
Release Date : 2017-08-04
Autonomic Nervous System written by Daniel Pedro Cardinali and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-04 with Medical categories.
A traditional view of the Autonomic Nervous System (ANS) considers only its peripheral part: the sympathetic and parasympathetic systems. However, this view misses to consider the most important ANS function: the maintenance of homeostasis. This term is used today to define not only the strategies that allow the body proper response to changes in the environment (reactive homeostasis), but also temporal mechanisms that allow the body to predict the most likely timing of environmental stimuli (predictive homeostasis based on biological rhythms). This book discusses the ANS from both an enlarged and a timed perspective. First, it presents how the organization of the ANS is hierarchical into different levels. Following that, the book discusses how the ANS changes functionally in the three-body configurations (wakefulness, slow sleep, rapid eye movement sleep) found in a 24-hour cycle. Finally, the most important clinical implications of this enlarged and timed vision of ANS will be discussed. Autonomic Nervous System – Basic and Clinical Aspects is a comprehensive text intended for medical students and health professionals who are interested in a deeper approach to this important part of the nervous system. It provides a detailed and complete understanding of the neuroscience behind the ANS, allowing a proper clinical applicability of this knowledge.
Brain Mechanisms International Colloquium Sponsored By The International Brain Research Organisation On Specific And Unspecific Mechanisms Of Sensory Motor Integration Pisa 1961
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Author : Giuseppe MORUZZI
language : en
Publisher:
Release Date : 1963
Brain Mechanisms International Colloquium Sponsored By The International Brain Research Organisation On Specific And Unspecific Mechanisms Of Sensory Motor Integration Pisa 1961 written by Giuseppe MORUZZI and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1963 with categories.
Tryptophan Metabolism Implications For Biological Processes Health And Disease
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Author : Atilla Engin
language : en
Publisher: Humana Press
Release Date : 2015-04-28
Tryptophan Metabolism Implications For Biological Processes Health And Disease written by Atilla Engin and has been published by Humana Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-04-28 with Medical categories.
This book discusses the relationship between cellular immunity and tryptophan metabolism, as well as its products, serotonin and melatonin, in the development of several diseases and reappraises the common signal transduction pathways of the neurodegenerative diseases, carcinogenesis, immune tolerance, inflammation, hypersensitivity reactions, neuropsychiatric disorders, in addition to bacterial tryptophan biosynthesis and novel antimicrobials. Tryptophan Metabolism: Implications for Biological Processes, Health and Disease presents fundamental information on tryptophan related metabolic pathways and metabolites, implications of these products for specific biological processes, diseases and conditions. This book focuses on effects of tryptophan metabolites on human health and will appeal to researchers, clinicians and students within this field.
Tertiary Lymphoid Structures
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Author : Marie-Caroline Dieu-Nosjean
language : en
Publisher: Humana Press
Release Date : 2018-09-05
Tertiary Lymphoid Structures written by Marie-Caroline Dieu-Nosjean and has been published by Humana Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-09-05 with Medical categories.
This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.