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GABAergic neurons provide most of the inhibitory drive of adult networks and play major roles in the integrative properties of brain networks. Alterations of GABAergic signals are associated with major neurological disorders and GABA mimetic drugs are widely used as comfort molecules and to treat several brain disorders. Thus, the inhibitory drive is altered in epilepsies, infantile developmentally related disorders but also Parkinson disease, and anoxo-ischemic insults to just name a few. From the developmental stand point, GABAergic neurons mature before principal neurons and provide an important source of early activities and are thus instrumental in activity dependent modulation of the construction of cortical functional units. The goal of this Research Topic is to bring together experts studying GABA signals at the molecular, cellular and network levels in physiological and pathological conditions and to examine the fate of GABA signals along transversal ideas linking these diverse domains. A particular emphasis is brain maturation as it is now clear that alteration of developmental sequences -notably of GABA signals- impairs brain development leading to life long deleterious neurological sequels. While this Frontiers Research Topic originated as a repository of work presented at CNCR Amsterdam, papers are invited from researchers continuing to work on this topic as the field expands.
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.
GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.
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 Gaba Receptors, Third Edition, presents a critical appraisal of our current understanding of the molecular, behavioral, biochemical, clinical, and pharmacological properties of GABA receptors. Emphasis is placed on exploring cutting-edge findings on the structureal properties of receptor sites, mechanisms of receptor expression, chemical agents that differentiate receptor subtypes, and phenotypes displayed by GABA receptor null mice. Chapters in this updated and expanded edition examine such topics as GABA receptor subypes, trafficking postsynaptic GABA receptors, GABA receptor mutations associated with idiopathic generalized epilepsies and febrile seizures, and GABA receptors as a potential therapeutic target.
Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.
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.
Pituitary Adenylate Cyclase-Activating Polypeptide is the first volume to be written on the neuropeptide PACAP. It covers all domains of PACAP from molecular and cellular aspects to physiological activities and promises for new therapeutic strategies. Pituitary Adenylate Cyclase-Activating Polypeptide is the twentieth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.
Receptor Endocytosis and Signalling in Health and Disease, Part B, Volume 196 highlights the different aspects of receptor endocytosis and signaling, covering several receptors which are associated with different organs and that play a key role in normal functioning in the body, including somatostatin, Mas receptor, AMPA, Dopamine, 5-HT1-2, GABA, GPCR, nuclear receptor, Integrin, BCR, CRHR1, etc. Chapters in this new release include Internalization of somatostatin receptors in brain and periphery, Mas receptor, signaling and trafficking in health and disease, Endocytosis of AMPA receptors: Role in neurological conditions, Endocytosis of dopamine receptor: Signaling in brain, and more. Additional chapters cover Endocytosis of LXRs: Signalling in liver, Endocytosis of LDL receptor: Importance in cardiovascular diseases, Advances in the molecular level understanding of G-protein-coupled receptor, Nuclear receptor: Structure and function, Integrin receptor trafficking in health and disease, B Cell Receptor (BCR) endocytosis,CRHR1 endocytosis: Spatiotemporal regulation of receptor signaling, and much more. - Provides information on the structure and function of nuclear receptors - Discusses the basic pathways involved in receptor internalization, subcellular trafficking, metabolic degradation, and signaling - Includes a wide range of neurological receptors and their roles