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 volume provides a comprehensive overview of recent advances in targeting glutamate signaling for the treatment of major psychiatric and neurological disorders. It draws on the latest findings in glutamate neurobiology and offers valuable insights into the application of translational principles in neuroscience drug discovery and development. In each chapter, glutamate as a neurotransmitter, its receptors and transporters, and their interplay with other neurotransmitters and neurotrophic factors, are discussed in the context of a specific, highly prevalent and disabling CNS disease. Most recent and detailed information is provided on Ischemic Stroke, Chronic Stress, Major Depressive Disorder, Bipolar Disorder, Autism Spectrum Disorders (ASD), Posttraumatic Stress Disorder (PTSD), Alzheimer’s Dementia, Schizophrenia, Impulsive Aggression, Substance Use Disorders (SUD), Amyotrophic Lateral Sclerosis (ALS), Chronic Pain, Multiple Sclerosis, Parkinson’s Disease, Attention Deficit Hyperactivity Disorder (ADHD), Migraine, Epilepsy and Anxiety disorders. Moreover, the book includes an extensive overview of glutamatergic treatments already available on the market, and those which are currently in pharmaceutical drug development pipelines. The primary beneficiaries will be neurology and psychiatry specialists and residents, neuroscientists, neuropharmacologists, pharmaceutical industry and clinical research organization professionals, academics, and clinicians working with psychiatric and neurological patients with comorbidities such as cardiologists, pulmonologists, and endocrinologists. This book will also appeal to psychiatry and neurology subspecialists and clinicians working in neuroscience labs seeking an easy-to-understand yet comprehensive overview of contemporary evidence-based clinical insights backed by basic science (preclinical) research evidence. Given its scope, the book is also a unique and indispensable resource for both preclinical and clinical neuroscientists, medical advisors, and clinical research specialists in the pharmaceutical industry. In addition, it will appeal to neuroscience and neuropsychopharmacology students and guide them through the complexities of glutamate involvement in the pathophysiology of the most common debilitating brain diseases with high unmet medical needs.

The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.

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 Advances in Pharmacology series presents a variety of chapters from the best authors in the field. - Includes the authority and expertise of leading contributors in pharmacology - Presents the latest release in the Advances in Pharmacology series

With the contribution from more than one hundred CNS neurotrauma experts, this book provides a comprehensive and up-to-date account on the latest developments in the area of neurotrauma including biomarker studies, experimental models, diagnostic methods, and neurotherapeutic intervention strategies in brain injury research. It discusses neurotrauma mechanisms, biomarker discovery, and neurocognitive and neurobehavioral deficits. Also included are medical interventions and recent neurotherapeutics used in the area of brain injury that have been translated to the area of rehabilitation research. In addition, a section is devoted to models of milder CNS injury, including sports injuries.

Neuropsychiatric diseases, such as schizophrenia, Alzheimer's disease, and etc., represent a serious medical and socioeconomic problems. These diseases are often accompanied by impairments of cognitive function, e.g., abstract thinking, decision-making, attention, and several types of memory. Such deficits significantly disrupt quality of life and daily functioning of patients. Cognitive deficits in neuropsychiatric diseases are associated with alterations of brain morphology and function, and are often resistant to therapeutic interventions. In schizophrenia and related disorders, cognitive deficits are also defined as endophenotypes, i.e. measurable phenotypes linking these disaeses with discrete heritable and reproducible traits. This points to the importance of elucidating these endophenotypes in translational studies. Animal models may not mimic the full spectrum of clinical symptoms, but may act as analogies of particular behaviors or other pathological outcomes. They are useful to search for the etiology of particular psychiatric illnesses and novel therapeutics. Moreover, several behavioral tests to measure cognitive performance in rodents and other species have been implemented. The primary focus of the present topic is to provide up-to-date information on cognitive deficits of neuropsychiatric disorders, such as schizophrenia. This Research Topic also delineates future directions for translational studies aimed at developing novel treatments/interventions of cognitive disturbances.

This book provides a clear and comprehensive guide to the clinical prescription of lithium that draws upon evidence-based knowledge of its mechanisms of action. The book is divided into two parts, on the science of lithium and the practice of lithium therapy. The former covers aspects such as the properties of the lithium ion, pharmacokinetics and pharmacodynamics, impact on neurotransmission, and gene expression modulation. The section on practice includes discussion of variability in response to lithium, use of lithium in the treatment of bipolar disorders, its value in suicide prevention, administration during pregnancy and in the pediatric age group, and side effects. Lithium is arguably the only true mood stabilizer, and its multifaceted effects across many clinical domains have given rise to a resurgence of interest in recent years, fuelled by both researchers and clinicians. Nevertheless, its use remains constrained by exaggerated concerns about potential side-effects. In reality, lithium is a simple molecule that is relatively straightforward to administer and monitor and has potentially profound benefits at a fraction of the cost of contemporary agents. This book dispels the many myths and concerns that surround its use and will be of interest for clinicians and researchers worldwide, and those that are recipients of lithium therapy.