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This contributed volume discusses the multiple roles of astrocytes, which determine the progression and outcome of neuropsychiatric diseases. This emerging area of study examines the ways in which astrocytes are involved in various aspects of disease initiation, progression and resolution. This monograph aims to integrate the body of information that has accumulated in recent years revealing the active role of astrocytes in neuropsychiatric pathology and in psychiatric disorders. Understanding roles of astrocytes in pathology will provide new targets for medical intervention and aid the development of much needed therapeutics. This book will be valuable for researchers and workers in the fields of neurobiology, neurology, and psychiatry, as well as fill the need for a textbook used in advanced courses/graduate seminars in glial pathophysiology.
Traditionally, abnormalities of neurons and neuronal networks including synaptic abnormalities and disturbance of neurotransmitters have dominantly been believed to be the main causes of psychiatric disorders. Recent cellular neuroscience has revealed various unknown roles of glial cells such as astrocytes, oligodendrocytes and microglia. These glial cells have proved to continuously contact with neurons /synapses, and have been shown to play important roles in brain development, homeostasis and various brain functions. Beyond the classic neuronal doctrine, accumulating evidence has suggested that abnormalities and disturbances of neuron-glia crosstalk may induce psychiatric disorders, while these mechanisms have not been well understood. This Research Topic of the Frontiers in Cellular Neuroscience will focus on the most recent developments and ideas in the study of glial cells (astrocytes, oligodendrocytes and microglia) focusing on psychiatric disorders such as schizophrenia, mood disorders and autism. Not only molecular, cellular and pharmacological approaches using in vitro / in vivo experimental methods but also translational research approaches are welcome. Novel translational research approaches, for example, using novel techniques such as induced pluripotent stem (iPS) cells, may lead to novel solutions. We believe that investigations to clarify the correlation between glial cells and psychiatric disorders contribute to a novel understanding of the pathophysiology of these disorders and the development of effective treatment strategies.
Neuropsychiatric disorders have long been considered as specific dysfunctions of neuronal functions. Studies of the recent decade, however, have challenged this simplistic view, highlighting the important role played by neuroglial cells in the onset and/or progression of neuropsychiatric diseases. In the central nervous system (CNS) non-excitable neuroglia are represented by cells of ectodermal origin (astrocytes, mainly responsible for CNS homeostasis and oligodendrocytes that provide myelination and support for axons) and mesodermal origin (microglial cells that are scions of foetal macrophages entering the neural tube early in development; these cells provide for CNS defence and contribute to shaping neuronal networks). Pathological changes of neuroglia are complex; these changes are classified into reactive gliosis (astrogliosis, activation of microglia and hypertrophy of oligodendroglial precursors), gliodegeneration with loss of function and glial pathological remodelling. Combination of these processes defines the evolution of neurological diseases in general and neuropsychiatric disorders in particular. In this research topic we addressed the contribution of neuroglia to major neuropsychiatric pathologies including major depression, schizophrenia, and addictive disorders.
Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodal, long-term memory, which is reinforced by -adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occurs at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.
This volume provides an introduction to the essential techniques required for studying the molecular biology of brain disease. The approaches and strategies for investigations of gene structure and regulation are described with reference to the molecular genetics of prion and Alzheimer's disease. The effects of aberrant gene regulation can also be examined at the protein level by immunocytochemistry and autoradiography. Improved understanding of basic biology has resulted in new approaches to animal models using transgenic techniques and new therapeutic approaches. The volume is structured to illustrate all these approaches and demonstrate the practice and promise of molecular neuropathology.
"This volume is a very valuable and much needed contribution." –Quarterly Review of Biology AT LAST - A comprehensive, accessible textbook on glial neurobiology! Glial cells are the most numerous cells in the human brain but for many years have attracted little scientific attention. Neurophysiologists concentrated their research efforts instead, on neurones and neuronal networks because it was thought that they were the key elements responsible for higher brain function. Recent advances, however, indicate this isn’t exactly the case. Not only are astroglial cells the stem elements from which neurones are born, but they also control the development, functional activity and death of neuronal circuits. These ground-breaking developments have revolutionized our understanding of the human brain and the complex interrelationship of glial and neuronal networks in health and disease. Features of this book: an accessible introduction to glial neurobiology including an overview of glial cell function and its active role in neural processes, brain function and nervous system pathology an exploration of all the major types of glial cells including: the astrocytes, oligodendrocytes and microglia of the ACNS and Schwann cells of the peripheral nervous system; the book also presents a broad overview of glial receptors and ion channels an investigation into the role of glial cells in various types of brain diseases including stroke, neurodegenerative diseases such as Alzheimer's, Parkinson's and Alexander's disease, brain oedema, multiple sclerosis and many more a wealth of illustrations, including unique images from the authors' own libraries of images, describing the main features of glial cells Written by two leading experts in the field, Glial Neurobiology provides a concise, authoritative introduction to glial physiology and pathology for undergraduate/postgraduate neuroscience, biomedical, medical, pharmacy, pharmacology, and neurology, neurosurgery and physiology students. It is also an invaluable resource for researchers in neuroscience, physiology, pharmacology and pharmaceutics.
The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography
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.
Major depression is a highly prevalent disorder that poses a significant social burden in society nowadays. The pathophysiology of this disease is still poorly understood but growing evidence suggests that impaired neuron and glial plasticity may be a key underlying mechanism for the precipitation of the disorder. One of the most surprising findings in this field was the involvement of glial cells in the pathophysiology of major depression and in the action of antidepressants, namely in mechanisms related with adult neurogenesis imbalances or dendritic arborization impairments. In particular, several works refer to alterations in the morphology and numbers of astrocytes, microglia and oligodendrocytes in the context of depression in human patients or animal models of depression. These observations were linked to functional evidences and suggested to underlie the pathophysiology of depression. Among others, these include impairments in the cross-talk between glia and neurons, changes in the level of neurotransmitter or immunoactive substances, myelination status, synapse formation, maintenance, or elimination. In addition to the implication of glia in the pathophysiology of depression, a number of studies is ascribing glia pathways to classically accepted antidepressant mechanisms. Therefore, it is noteworthy to elucidate the role of glia in the effect provided by antidepressant treatment in order to better understand secondary effects and elucidate alternative targets for treatment.
Glial Physiology and Pathophysiology provides a comprehensive, advanced text on the biology and pathology of glial cells. Coverae includes: the morphology and interrelationships between glial cells and neurones in different parts of the nervous systems the cellular physiology of the different kinds of glial cells the mechanisms of intra- and inter-cellular signalling in glial networks the mechanisms of glial-neuronal communications the role of glial cells in synaptic plasticity, neuronal survival and development of nervous system the cellular and molecular mechanisms of metabolic neuronal-glial interactions the role of glia in nervous system pathology, including pathology of glial cells and associated diseases - for example, multiple sclerosis, Alzheimer's, Alexander disease and Parkinson's Neuroglia oversee the birth and development of neurones, the establishment of interneuronal connections (the 'connectome'), the maintenance and removal of these inter-neuronal connections, writing of the nervous system components, adult neurogenesis, the energetics of nervous tissue, metabolism of neurotransmitters, regulation of ion composition of the interstitial space and many, many more homeostatic functions. This book primes the reader towards the notion that nervous tissue is not divided into more important and less important cells. The nervous tissue functions because of the coherent and concerted action of many different cell types, each contributing to an ultimate output. This reaches its zenith in humans, with the creation of thoughts, underlying acquisition of knowledge, its analysis and synthesis, and contemplating the Universe and our place in it. An up-to-date and fully referenced text on the most numerous cells in the human brain Detailed coverage of the morphology and interrelationships between glial cells and neurones in different parts of the nervous system Describes the role og glial cells in neuropathology Focus boxes highlight key points and summarise important facts Companion website with downloadable figures and slides