Astrocytic Neuronal Astrocytic Pathway Selection For Formation And Degradation Of Glutamate Gaba
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Astrocytic-neuronal-astrocytic Pathway Selection for Formation and Degradation of Glutamate/GABA by Leif Hertz,Tiago B. Rodrigues Pdf
Endocrinological research early recognized the importance of intercellular interactions and realized the importance of glutamatergic and GABAergic signaling. In turn this signalling depends on elaborate interactions between astrocytes and neurons, without which neurons would be unable to produce, reuse and metabolize transmitter glutamate and GABA. Details of these subjects are described in this Research Topic by key investigators in this field. It focuses on the intricate and extremely swift pathway producing these amino acid transmitters from glucose in brain but also discusses difficulties in determining expression of some of the necessary genes in astrocytes and related processes in pancreatic islets. However, it does not discuss how closely associated astrocytes and neurons are anatomically, enabling these interactions. This is elegantly shown in this cover image, kindly provided by Professor Andreas Reichenbach (University of Leipzig, Germany).
The Glutamate/GABA-Glutamine Cycle by Arne Schousboe,Ursula Sonnewald Pdf
Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.
The second volume of the Handbook does not parallel any volume of the first edition; it is one more sign, or reflection, of the expansion of the field. By emphasizing the experimental approach, it illustrates the tools that have re cently become available for investigating the nervous system. Also, perhaps even more than other volumes, it illustrates the multidisciplinary nature of the field, requiring multidisciplinary methodology. It is now recognized that the availability of methodology is often the rate-limiting determinant of studies and that improvements or innovations in instrumentation can open up new avenues. A new improved method, although opening up new possibilities and being crucial to making advances, is only a tool whose use will determine its use fulness. If we do not recognize its possibilities, its use will be limited; if we do not recognize its limitations, it will mislead us. It is the possibilities and limitations and the results obtained that are illustrated here.
Glycolysis at 75: Is it Time to Tweak the First Elucidated Metabolic Pathway in History? by Avital Schurr,Evelyne Gozal Pdf
Glycolysis, the pathway of enzymatic reactions responsible for the breakdown of glucose into two trioses and further into pyruvate or lactate, was elucidated in 1940. For more than seven decades, it has been taught precisely the way its sequence was proposed by Embden, Meyerhof and Parnas. Accordingly, two outcomes of this pathway were proposed, an aerobic glycolysis, with pyruvate as its final product, and an anaerobic glycolysis, identical to the aerobic one, except for an additional reaction, where pyruvate is reduced to lactate. Several studies in the 1980s have shown that both muscle and brain tissues can oxidize and utilize lactate as an energy substrate, challenging this monocarboxylate’s reputation as a useless end-product of anaerobic glycolysis. These findings were met with great skepticism about the idea that lactate could be playing a role in bioenergetics. In the past quarter of a century monocarboxylate transporters (MCTs) were identified and localized in both cellular and mitochondrial membranes. A lactate receptor has been identified. Direct and indirect evidence now indicate that the enzyme lactate dehydrogenase (LDH) resides not only in the cytosol, as part of the glycolytic pathway machinery, but also in the mitochondrial outer membrane. The mitochondrial form of the enzyme oxidizes lactate to pyruvate and concomitantly produces the reducing agent NADH. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway i.e., its inability to regenerate NAD+, as opposed to anaerobic glycolysis that features the cyclical ability of regenerating NAD+ upon pyruvate reduction to lactate by the cytosolic form of LDH. The malate-aspartate shuttle (MAS), a major redox shuttle in the brain, was proposed as an alternative pathway for NAD+ generation for aerobic glycolysis. Nonetheless, would MAS really be necessary for that function if glycolysis always proceeds to the end-products, lactate and NAD+? An additional dilemma the originally proposed aerobic glycolysis presents has to do with the glycolytic pathway of erythrocytes, which despite its highly aerobic environment, always produces lactate as its end-product. It is time to reexamine the original, dogmatic separation of glycolysis into two distinct pathways and put to test the hypothesis of a unified, singular pathway, the end-product of which is lactate, the real substrate of the mitochondrial TCA cycle.
Astrocytes in (Patho)Physiology of the Nervous System by Vladimir Parpura,Philip G. Haydon Pdf
Astrocytes were the original neuroglia that Ramón y Cajal visualized in 1913 using a gold sublimate stain. This stain targeted intermediate filaments that we now know consist mainly of glial fibrillary acidic protein, a protein used today as an astrocytic marker. Cajal described the morphological diversity of these cells with some ast- cytes surrounding neurons, while the others are intimately associated with vasculature. We start the book by discussing the heterogeneity of astrocytes using contemporary tools and by calling into question the assumption by classical neuroscience that neurons and glia are derived from distinct pools of progenitor cells. Astrocytes have long been neglected as active participants in intercellular communication and information processing in the central nervous system, in part due to their lack of electrical excitability. The follow up chapters review the “nuts and bolts” of ast- cytic physiology; astrocytes possess a diverse assortment of ion channels, neu- transmitter receptors, and transport mechanisms that enable the astrocytes to respond to many of the same signals that act on neurons. Since astrocytes can detect chemical transmitters that are released from neurons and can release their own extracellular signals there is an increasing awareness that they play physiological roles in regulating neuronal activity and synaptic transmission. In addition to these physiological roles, it is becoming increasingly recognized that astrocytes play critical roles during pathophysiological states of the nervous system; these states include gliomas, Alexander disease, and epilepsy to mention a few.
This book collates the contributions of a selected number of neuroscientists that are interested in the molecular, preclinical, and clinical aspects of neurotransmission research. The seven chapters in this book address the latest research/review data related to GABA/glutamate system's organization and function, the structure of receptors, subtypes and their ligands, as well as the translational approach and clinical implications. The book offers readers a rich collection of data regarding current and future applications of GABA and glutamate neurotransmission, including promising research strategies and potential clinical benefits.
Astrocyte by Maria Teresa Gentile,Luca Colucci D’Amato Pdf
A team of authors from prestigious academic schools contributed to draw up a project that would give a detailed account of astrocyte's morphology and physiology, examining thoroughly all the astrocyte's types; giving an accurate description of their morphology, location, function in the brain; and illustrating their physiology and pathology in terms of dealing with neurons through "gliotransmitters," ionic channels, and membrane receptors expression. This book gives an overview of the crucial role of astrocytes in the physiology of the CNS and in the pathogenesis of several CNS disorders suggesting that the shift from a neurocentric view to one that incorporates astrocytes in disease models for drug discovery is a critical step in renewing drug development strategies to treat neurodegenerative diseases.
Brain Energy Metabolism by Johannes Hirrlinger,Helle S. Waagepetersen Pdf
Brain Energy Metabolism addresses its challenging subject by presenting diverse technologies allowing for the investigation of brain energy metabolism on different levels of complexity. Model systems are discussed, starting from the reductionist approach like primary cell cultures which allow assessing of the properties and functions of a single brain cell type with many different types of analysis, however, at the expense of neglecting the interaction between cell types in the brain. On the other end, analysis in animals and humans in vivo is discussed, maintaining the full complexity of the tissue and the organism but making high demands on the methods of analysis. Written for the popular Neuromethods series, chapters include the kind of detailed description and key implementation advice that aims to support reproducible results in the lab. Meticulous and authoritative, Brain Energy Metabolism provides an ideal guide for researchers interested in brain energy metabolism with the hope of stimulating more research in this exciting and very important field.
This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.
Patterning and Cell Type Specification in the Developing CNS and PNS by Anonim Pdf
The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development and on new psychiatric/neurological treatments being developed based on our increased understanding of developmental mechanisms. Each volume in the series consists of review style articles that average 15-20pp and feature numerous illustrations and full references. Volume 1 offers 48 high level articles devoted mainly to patterning and cell type specification in the developing central and peripheral nervous systems. Series offers 144 articles for 2904 full color pages addressing ways in which the nervous system and its components develop Features leading experts in various subfields as Section Editors and article Authors All articles peer reviewed by Section Editors to ensure accuracy, thoroughness, and scholarship Volume 1 sections include coverage of mechanisms which: control regional specification, regulate proliferation of neuronal progenitors and control differentiation and survival of specific neuronal subtypes, and controlling development of non-neural cells
Jasper's Basic Mechanisms of the Epilepsies by Jeffrey L. Noebels,Massimo Avoli Pdf
Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
Translational Research in Traumatic Brain Injury by Daniel Laskowitz,Gerald Grant Pdf
Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the development of new diagnostic and therapeutic approaches has been disappointingly slow. Translational Research in Traumatic Brain Injury attempts to integrate expertise from across specialties to address knowledge gaps in the field of TBI. Its chapters cover a wide scope of TBI research in five broad areas: Epidemiology Pathophysiology Diagnosis Current treatment strategies and sequelae Future therapies Specific topics discussed include the societal impact of TBI in both the civilian and military populations, neurobiology and molecular mechanisms of axonal and neuronal injury, biomarkers of traumatic brain injury and their relationship to pathology, neuroplasticity after TBI, neuroprotective and neurorestorative therapy, advanced neuroimaging of mild TBI, neurocognitive and psychiatric symptoms following mild TBI, sports-related TBI, epilepsy and PTSD following TBI, and more. The book integrates the perspectives of experts across disciplines to assist in the translation of new ideas to clinical practice and ultimately to improve the care of the brain injured patient.
Molecular and Cellular Neurobiology by S. Prasad Pdf
Presents an account of the remarkable progress made in different areas of neurobiology. This book introduces the structure and development of the brain, showing how they are specialized for the functions they serve. It is concerned with hormones and neurotransmitters.
Synaptic Function by Neurosciences Institute (New York, N.Y.) Pdf
This book consists of five sections. The first section details methods for analyzing both presynaptic and postsynaptic function and emphasizes the molecular aspects of synapses. It describes ongoing studies of neurotransmitter release, voltage- sensitive ion channels, and electronic transmission at gap junctions. The second section focuses on the growing menagerie of neurotransmitters: their catagorization into chemical families, their relation to ion channels, their modulation by second messenger systems and their role in pharmacologic action. The third section considers the important relationship of transmitter diversity and synaptic types to the behavior of actual cellular networks. All of the studies described in these sections point to the necessity of considering interactions between anatomy, chemistry, physiology and pharmacology if synaptic function is to be understood at any one of these levels of analysis.
Computational Glioscience by Maurizio De Pittà,Hugues Berry Pdf
Over the last two decades, the recognition that astrocytes - the predominant type of cortical glial cells - could sense neighboring neuronal activity and release neuroactive agents, has been instrumental in the uncovering of many roles that these cells could play in brain processing and the storage of information. These findings initiated a conceptual revolution that leads to rethinking how brain communication works since they imply that information travels and is processed not just in the neuronal circuitry but in an expanded neuron-glial network. On the other hand the physiological need for astrocyte signaling in brain information processing and the modes of action of these cells in computational tasks remain largely undefined. This is due, to a large extent, both to the lack of conclusive experimental evidence, and to a substantial lack of a theoretical framework to address modeling and characterization of the many possible astrocyte functions. This book that we propose aims at filling this gap, providing the first systematic computational approach to the complex, wide subject of neuron-glia interactions. The organization of the book is unique insofar as it considers a selection of “hot topics” in glia research that ideally brings together both the novelty of the recent experimental findings in the field and the modelling challenge that they bear. A chapter written by experimentalists, possibly in collaboration with theoreticians, will introduce each topic. The aim of this chapter, that we foresee less technical in its style than in conventional reviews, will be to provide a review as clear as possible, of what is “established” and what remains speculative (i.e. the open questions). Each topic will then be presented in its possible different aspects, by 2-3 chapters by theoreticians. These chapters will be edited in order to provide a “priming” reference for modeling neuron-glia interactions, suitable both for the graduate student and the professional researcher.