Glial Neurobiology - ACh acetylcholine AIDS acquired immunodeficiency syndrome AMPA -amino-3-hydroxy-5-methyl

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  • Glial Neurobiology A Textbook

    Alexei Verkhratsky University of Manchester

    Arthur Butt University of Portsmouth

  • Copyright © 2007 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England

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    Library of Congress Cataloging in Publication Data

    Verkhratskii, A. N. (Aleksei Nestorovich) Glial neurobiology : a textbook / Alexei Verkhratsky, Arthur Butt.

    p. ; cm. Includes bibliographical references and index. ISBN 978-0-470-01564-3 (cloth : alk. paper) 1. Neuroglia. I. Butt, Arthur. II. Title. [DNLM: 1. Neuroglia. WL 102 V519g 2007] QP363.2.V47 2007 611′ .0188—dc22 2007015819

    British Library Cataloguing in Publication Data

    A catalogue record for this book is available from the British Library

    ISBN 978-0-470-01564-3 (HB) ISBN 978-0-470-51740-6 (PB)

    Typeset in 10.5/12.5pt Times by Integra Software Services Pvt. Ltd, Pondicherry, India Printed and bound in Great Britain by Antony Rowe Ltd, Chippenham, Wiltshire This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production.

  • Contents

    Preface xi

    List of abbreviations xiii

    PART I Physiology of Glia 1

    1 Introduction to Glia 3 1.1 Founders of glial research: from Gabriel Valentin to Karl-Ludwig Schleich 3 1.2 Beginning of the modern era 11 1.3 Changing concepts: Glia express molecules of excitation 11 1.4 Glia and neurones in dialogue 12

    2 General Overview of Signalling in the Nervous System 13 2.1 Intercellular signalling: Wiring and volume modes of transmission 13 2.2 Intracellular signalling 17

    3 Morphology of Glial Cells 21 3.1 Astrocytes 21 3.2 Oligodendrocytes 24 3.3 NG2 expressing glia 26 3.4 Schwann cells 27 3.5 Microglia 28

    4 Glial Development 29 4.1 Phylogeny of glia and evolutionary specificity of glial cells in human brain 29 4.2 Macroglial cells 32 4.3 Astroglial cells are brain stem cells 35 4.4 Schwann cell lineage 36 4.5 Microglial cell lineage 37

    5 General Physiology of Glial Cells 39 5.1 Membrane potential and ion distribution 39 5.2 Ion channels 39 5.3 Receptors to neurotransmitters and neuromodulators 42 5.4 Glial syncytium – gap junctions 58

  • viii CONTENTS

    5.5 Glial calcium signalling 61 5.6 Neurotransmitter release from astroglial cells 71 5.7 Glial neurotransmitter transporters 76 5.8 Glial cells produce and release neuropeptides 79 5.9 Glial cell derived growth factors 80

    6 Neuronal–Glial Interactions 83 6.1 Close apposition of neurones and astroglia: the tripartite synapse 83 6.2 Neuronal–glial synapses 85 6.3 Signalling from neurones to astrocytes 86 6.4 Signalling from astrocytes to neurones 89 6.5 Signalling between oligodendrocytes and neurones 90 6.6 Signalling between Schwann cells and peripheral nerves and nerve

    endings 90

    PART II Glial Cells and Nervous System Function 93

    7 Astrocytes 95

    7.1 Developmental function – producing new neural cells 96 7.2 Developmental function – neuronal guidance 97 7.3 Regulation of synaptogenesis and control of synaptic maintenance and

    elimination 99 7.4 Structural function – creation of the functional microarchitecture of the

    brain 101 7.5 Vascular function – creation of glial–vascular interface (blood–brain

    barrier) and glia–neurone–vascular units 102 7.6 Regulation of brain microcirculation 105 7.7 Ion homeostasis in the extracellular space 106 7.8 Regulation of extracellular glutamate concentration 112 7.9 Water homeostasis and regulation of the extracellular space volume 114 7.10 Neuronal metabolic support 116 7.11 Astroglia regulate synaptic transmission 119 7.12 Integration in neuronal–glial networks 121 7.13 Astrocytes as cellular substrate of memory and consciousness? 121

    8 Oligodendrocytes, Schwann Cells and Myelination 125 8.1 The myelin sheath 127 8.2 Myelination 141 8.3 Myelin and propagation of the action potential 148

    PART III Glia and Nervous System Pathology 153

    9 General Pathophysiology of Glia 155 9.1 Reactive astrogliosis 155 9.2 Wallerian degeneration 157 9.3 Activation of microglia 160


    10 Glia and Diseases of the Nervous System 167 10.1 Alexander’s disease 167 10.2 Spreading depression 167 10.3 Stroke and ischaemia 168 10.4 Cytotoxic brain oedema 178 10.5 Neurodegenerative diseases 180 10.6 Neuropathic pain 185 10.7 Demyelinating diseases 186 10.8 Infectious diseases 187 10.9 Peripheral neuropathies 190 10.10 Psychiatric diseases 192 10.11 Gliomas 194

    Conclusions 197

    Recommended literature 199

    Author Index 207

    Subject Index 209

  • Preface

    Contemporary understanding of brain organization and function follows the neuronal doctrine, which places the nerve cell and neuronal synaptic contacts at the very centre of the nervous system. This doctrine considers glia as passive supportive cells, which are not involved in the informational exchange, and there- fore secondary elements of the nervous system.

    In the last few decades, however, our perception of the functional organiza- tion of the brain has been revolutionized. New data forces us to reconsider the main postulate of the neuronal doctrine – that neurones and synapses are the only substrate of integration in the central nervous system. We now learn that astroglial cells, which are the most numerous cells in the brain, literally control the naissance, development, functional activity and death of neuronal circuits. Astroglial cells are in fact the stem elements from which neurones are born. They also create the compartmentalization of the CNS and integrate neurones, synapses, and brain capillaries into inter-dependent functional units. Furthermore, astroglial cells form a functional syncytium, connected through gap junction bridges, which provides an elaborate intercellular communication route. This allows direct translo- cation of ions, metabolic factors and second messengers throughout the CNS, thereby providing a sophisticated means for information exchange. In a way the binary coded electrical communication within neuronal networks may be consid- ered as highly specialized for rapid conveyance of information, whereas astroglial cells may represent the true substance for information processing, integration and storage. Will this truly heretical theory which subordinates neurones to glia be victorious at the end? Forthcoming years hold the answer.

    When writing this book we have attempted to create a concise yet comprehensive account of glial cells and their role in physiology and pathology of the nervous system. We hope very much that this account may help the reader to discover a fascinating world of brain ‘secondary’ cells, which in fact are essential elements of the nervous system, whose functions and importance are yet to be fully appreciated.

    Alexei Verkhratsky Arthur Butt

  • List of abbreviations

    AC adenylate cyclase

    ACh acetylcholine

    AIDS acquired immunodeficiency syndrome

    AMPA �-amino-3-hydroxy-5-methyl-�-isoxazolepropionate

    AQP aquaporins (water channels)

    ATP adenosine triphosphate

    BDNF brain-derived neurotrophic factor

    BK bradykinin

    cAMP cyclic adenosine monophosphate

    cGMP cyclic guanosine monophosphate

    CaV voltage-gated calcium channels

    CNP 2