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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 provides a new compilation of information that link changes in the basic structure of synapses and brain diseases. The book shows that specific secreted proteins, and short peptide mimicking the function of neural cell adhesion molecules can significantly enhance the formation of synapses in the brain. It describes recent advances in research that lay necessary scientific groundwork to develop pharmacological treatments.
A comprehensive, multidisciplinary review, Neural Plasticity and Memory: From Genes to Brain Imaging provides an in-depth, up-to-date analysis of the study of the neurobiology of memory. Leading specialists share their scientific experience in the field, covering a wide range of topics where molecular, genetic, behavioral, and brain imaging techniq
As the most abundant excitatory neurotransmitter in the brain, glutamate plays an important role in numerous aspects of normal and pathological brain function. This book provides an overview of the role of metabotropic glutamate receptors (mGluRs) in basic brain functioning, such as autonomic regulation, synaptic plasticity, and learning and memory. Also provided are up-to-date summaries of recent progress towards identifying how mGluRs both mediate and represent novel pharmacotherapeutic targets for the treatment of various neurological and neuropsychiatric disorders, such as depression, anxiety, schizophrenia, amyloidogenic disorders and substance abuse.
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 developme
The volume presents a comprehensive and up-to-date treatise of the glutamatergic synapse and its environment. Particular emphasis is on the localizations of the molecular constituents of the synaptic machinery. Immunogold and other high-resolution methods are used extensively. Each chapter presents new data that have not previously been reviewed. The material presented forms the basis for work directed to understanding the functional properties of excitatory synapses in greater depth, to discover mechanisms of neurological and psychiatric disorders and novel methods for treatment. Chapter 1 deals with the transmitter molecule itself, mechanisms of release and pathways for glutamate synthesis. The anatomy of glutamatergic nerve projection pathways in different brain regions is dealt with. In Chapter 2, focus is on aspartate, the enigmatic congener of glutamate, and its possible role in excitatory neurotransmission. Chapters 3 through 6 deal with glutamate receptors. Metabotropic glutamate receptors are presented in Chapter 3. Chapter 4 presents an in situ hybridization atlas of the different classes of ionotropic glutamate receptors. The localizations of these receptors at the regional and synaptic level are presented in Chapter 5. The ways in which the receptors are brought to the synapse and held in position are the subject of Chapter 6. Chapter 7 deals with the enzymes responsible for formation and catabolism of glutamate. In Chapter 8, the regulation of extracellular glutamate levels by glutamate transporters is discussed. The final two chapters of the volume focus on two "model synapses" that, due to special features, lend themselves particularly well to demonstrating properties of glutamatergic synapses. The hair cell-to-afferent nerve terminal synapses in the inner ear (Chapter 9), with their supporting cells, share essential properties with glutamatergic synapses in the central nervous system. The salient features of the latter are illustrated by the synapses of the giant reticulo-spinal axons of the lamprey, used to unravel molecular mechanisms of the cycling of synaptic vesicles (Chapter 10)
This book provides the reader with background information on neurotransmitter release. Emphasis is placed on the rationale by which proteins are assigned specific functions rather than just providing facts about function.
The synapse is a fascinating structure for many reasons. Biologically, it is an exquisitely organized subcellular compartment that has a remarkable capacity for fidelity and endurance. Computationally, synapses play a central role in signal transmission and processing that represent evolution s solution to learning and memory. Nervous systems, including our own brains, possess an extraordinary capacity for adaptation and memory because the synapse, not the neuron, constitutes the basic unit for information storage. Because the molecular complexities underlying signal processing and information storage must occur within the tiny space of the synapse, the precise molecular organization of proteins, lipids, and membranes at the synapse is paramount. Given the central role of the synapse in neuronal communication, it comes as no surprise that dysregulation of the synapse accounts for many, if not most, neurological and psychiatric disorders. Clinically, the synapse thus constitutes a prime target for treatments of these diseases. It is for these reasons that we have chosen to focus our work on deciphering the structural and functional organization of the synapse. We have assembled leaders in the field of synapse biology to describe and distill the wonders and mysteries of the synapse. This book provides a fundamental description of the synapse developed over many decades by numerous investigators, paired with recent insight into new aspects of synapse structure and function that is still in flux and at the cutting edge of research."