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Timiras, MD, PhD University of California at Berkeley, Berkeley, CA Springer Science+Business Media, LLC Dedication for Antonia Vernadakis © 2002 Springer S cience +Bu.siness Media New York Originally published by Humana Press Inc in 2002 Softcover reprint of the hardcover 1st edition 2002 All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. All authored papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. This publication is printed on acid-free paper. ∞ ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Production Editor: Mark J. Breaugh. Cover design: Patricia Cleary. Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Springer Science+Business Media, LLC, provided that the base fee of US $10.00 per copy, plus US $00.25 per page, is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Springer Science+Business Media, LLC. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging in Publication Data Neuroglia in the aging brain / edited by Jean S. de Vellis. p. ; cm. -- (Contemporary neuroscience) Includes bibliographical references and index. 1. Neuroglia. 2. Brain--Aging. 3. Brain--Aging--Molecular aspects. I. De Vellis, Jean II. Series. [DNLM: 1. Brain--cytology. 2. Neuroglia--physiology. 3. Aging--physiology. 4. Neurodegenerative Diseases. WL 300 N4938154 2001] QP363.2 .N483 2001 612.8'2--dc21 2001026438 59-105-3 ISBN 978-1-61737-088-5 ISBN 978-1-59259-105-3 (eBook) DOI 10.1007/978-1-59259-105-3 Foreword As we begin the second millennium and evaluate human achievements, one of the greatest accomplishments of civilization is unquestionably the extraordinary increase of human life expectancy. In prehistoric and early historic times, the average span of life was as short as 25 years. In 1900, a child born in the United States might expect to live only about 50 years, given the mortality conditions of the time. Currently, in most developed countries, life expectancy has risen to around 75 to 80 years. Thus, about half of the remarkable increase in life expectancy has taken place during the 20th century. Many factors have contributed to this rapid and unprecedentedchange, among which may be listed not only advances in biomedical sciences (e.g., dis- covery and use of antibiotics, an understanding of the structure of DNA and the gene), but also improvements in socioeconomic conditions (e.g., higher incomes, better access to medical/health care, better sanitation). One result has been the rapid aging of human populations. Now, greater numbers of individuals are surviving to become centenarians, with ages that approach or even exceed those thought previously to represent the maximal potential life span. Moreover, human life span appears still to continue to lengthen. Given the rapidly increasing proportion of the aged in thepresent popu- lation, especially those 80 years and older, it is important to understand the physiopathology of aging to be able to improve and prolong functional compe- tence and to prevent or treat the disabilities and diseases of old age. Despite numerous theories of aging at themolecular level [e.g., genetic mutations, DNA damage and faulty repair, expression of genes (gerontogenes, longevity assur- ance genes) promoting or inhibiting cell proliferation, and role of telomeres], at the cellular level (e.g., wear and tear, oxidative damage), and the organismic level (e.g., disruption of neuro-immuno-endocrine interactions), the cause(s) and nature of the aging process remain elusive. In complex organisms (mammals and especially humans), the central nervous system, closely related to the immune and endocrine systems, plays a key role in regulating the various stages of the life-span from early development to childhood, adulthood, and old age. Thus, alterations in the nervous system associated with age, such as may occur in neurodegenerative diseases, may impair the capacity of the affected individual to adapt to environmental demands, weaken physiologic competence, and induce death. Aging-associated changes in neural structures and metabolism, synapses and neurotransmission, cell num- ber and regeneration, growth-promoting or inhibiting factors, all play a crucial role in endowing the nervous system with a certain degree of plasticity. Plasticity in this sense is the capacity to show compensatory/adaptive responses on demand (e.g., generated by environmental stimuli/damage). This property, until 20–30 years ago, considered a privilege of the developing nervous system, is now viewed as potentially extended to include the adult and even the old central nervous system. v vi Foreword Indeed, the study of the aging nervous system and, particularly, of neu- rons, is one of the most active areas of research in the field of gerontology and geriatrics. Less well-known are changes with aging in glial cells and the factors that may modulate aging of these cells. However, it is expected that knowledge of the importance of glial cells in their relation to neuronal metabolism and transport (astrocytes), to myelin formation (oligodendrocytes), and as repre- sentative of the immune system (microglia) will become considerably enhanced in the near future. With increasing progress in central nervous system rehabili- tation, the restoration of neuronal plasticity after damage caused by trauma, disease, or aging is becoming a reachable reality. Although adult neurons usu- ally do not proliferate, this does not necessarily signify that they have lost the capacity to divide; perhaps inhibitory factors derived from the matrix or even the glial cells prevent adult neurons from manifesting this property. Such inhibition of cell division would ensure neuronal stability desirable for optimal nervous system function. However, under appropriate endogenous influences of their microenvironment, neurons may regenerate, not only in rodents and primates, but also in human brains. Because glial cells with the intercellular matrix and the blood vessels comprise this microenvironment, it may be argued that the study of factors that influence glial function represents a promising, albeit indirect, approach to eventual therapeutic manipulation of neuronal potential for self- renewal. Keeping this important role of neuroglia in mind, Neuroglia in the Aging Brainhas been organized around six major topics. First to be examined are the cellular and molecular changes that occur with aging, especially in astro- cytes, the aging-associated gliosis and its relation to neuronal injury and repair. This is followed by a discussion of neuron–glia intercommunication and of how glial signals may be modified/modulated by neurohormones, hormones, extra- and intracellular metabolism and transport, as well as aging of the blood–brain barrier. The last chapters examine the role of neuroglia, especially that of astro- cytes, in the etiology of a number of neurodegenerative diseases and evaluate possible therapeutic interventions, specifically on glial responses, but also, indi- rectly on neurons. Planning for this book was envisioned first by Dr. Antonia Vernadakis to whom the book is dedicated. She outlined the major topics to be considered, she enlisted the majority of the contributors and secured a publisher. However, her death in 1998, brought the preparation of the book to a halt and threatened its future completion. The book contributors, well aware of the basic and practical significant contribution of glial development, function and aging to CNS plastic- ity, were eager to see the book published. Therefore, I know that I express the feelings of all contributors, including my own, when I gratefully acknowledge the willingness of Dr. Jean De Vellis to take over the task of editing the book, which he has done with great expertise. We are also grateful to Elyse O'Grady from Humana Press for her steadfast support of the book publication. Paola S. Timiras Preface The study of the neuroscience and neurobiology of aging continues to be an intensely active area of research. However, most of the research has been conducted on neurons. Neuroglia in the Aging Brain reviews the current knowl- edge of the supporting structure of the nervous system, the neuroglia, in aging. Neuroglia in the Aging Brain discusses the role of glial cells in normal aging and in pathological aging, i.e., neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, because a great deal of knowledge can be gleaned from the study of these more severe forms of aging. The book is divided into six sections: cellular and molecular changes of aged and reactive astrocytes; neuron–glia intercommunication; neurotrophins, growth factors, and neurohor- mones in aging and regeneration; metabolic changes; astrocytes and the blood– brain barrier in aging; and astrocytes in neurodegenerative diseases. It is my hope that all of those scientists engaged in this interesting area of research will find this book to be useful. Many thanks to all of the authors for their fine contributions. Jean S. de Vellis vii Contents Foreword by Paola Timiras.......................................................................................v Preface........................................................................................................................ vii Contributors............................................................................................................. xiii PART I. CELLULARAND MOLECULAR CHANGESOF AGED AND REACTIVE ASTROCYTES 1 •Neuromorphological Changes in Neuronal and Neuroglial Populations of the Cerebral Cortex in the Aging Rat: Neurochemical Correlations.............................................................................3 Maria Angeles Peinado, Manuel Martinez, Maria Jesus Ramirez, Adoracion Quesada, Juan Angel Pedrosa, Concepcion Iribar, and Jose Maria Peinado 2 • Diversity in Reactive Astrocytes...................................................................17 Sudarshan K. Malhotra and Theodor K. Shnitka 3 • Astrocytic Reaction After Traumatic Brain Injury.....................................35 Jesús Boya, J. L. Calvo, Angel López-Carbonell, and José E. García-Mauriño PART II. NEURON–GLIA INTERCOMMUNICATION 4 • Astrocytes In Situ Exhibit Functional Neurotransmitter Receptors.......59 Marilee K. Shelton and Ken D. McCarthy 5 • Glia and Extracellular Space Diffusion Parameters in the Injured and Aging Brain............................................77 Eva Syková 6 • Intercellular Diffusional Coupling between Glial Cells in Slices from the Striatum.........................................................................................99 Brigitte Hamon, Jacques Glowinski, and Christian Giaume 7 • Glial Cell Involvement in Brain Repair and the Effects of Aging.........113 Elizabeth A. Howes and Peter J. S. Smith 8 • ATP Signaling in Schwann Cells.................................................................135 Thierry Amédée, Aurore Colomar, and Jonathan A. Coles PART III. NEUROTROPHINS, GROWTH FACTORS, AND NEUROHORMONES IN AGING AND REGENERATION 9 • Gliosis Growth Factors in the Adult and Aging Rat Brain .......................157 Gérard Labourdette and Françoise Eclancher 10 • Role of Fibroblast Growth Factor-2 in Astrogliosis.................................179 John F. Reilly 11 • Trophins as Mediators of Astrocyte Effects in the Aging and Regenerating Brain............................................................................199 Judith Lackland and Cheryl F. Dreyfus ix x Contents 12 • Responses in the Basal Forebrain Cholinergic System to Aging .......217 Zezong Gu and J. Regino Perez-Polo 13 • Effects of Estrogens and Thyroid Hormone on Development and Aging of Astrocytes and Oligodendrocytes .................................245 Kevin Higashigawa, Alisa Seo, Nayan Sheth, Giorgios Tsianos, Hogan Shy, Latha Malaiyandi, and Paola S. Timiras PART IV. METABOLIC CHANGES 14 • Neurotoxic Injury and Astrocytes ..............................................................259 Michael Aschner and Richard M. LoPachin 15 • Ammonium Ion Transport in Astrocytes: Functional Implications ........275 Neville Brookes PART V. ASTROCYTES AND THE BLOOD-BRAIN BARRIERIN AGING 16 • Molecular Anatomy of the Blood-Brain Barrier in Development and Aging......................................................................291 Dorothee Krause, Pedro M. Faustmann, and Rolf Dermietzel 17 • The Blood-Brain Barrier in the Aging Brain..............................................305 Gesa Rascher and Hartwig Wolburg 18 • Astrocytes and Barrier-provided Microvasculature in the Developing Brain............................................................................321 Luisa Roncali PART VI. ASTROCYTESIN NEURODEGENERATIVE DISEASES 19 • Microglial and Astrocytic Reactions in Alzheimer's Disease.....................339 Douglas G. Walker and Thomas G. Beach 20 • Activated Neuroglia in Alzheimer's Disease ............................................365 Kurt R. Brunden and Robert C. A. Frederickson 21 • Reactive Astroglia in the Ataxic Form of Creutzfeldt-Jakob Disease: Cytology and Organization in the Cerebellar Cortex.....................................375 Miguel Lafarga, Nuria T. Villagra, and Maria T. Berciano 22 • Ischemic Injury, Astrocytes, and the Aging Brain...................................393 Robert Fern 23 • Glial-Neuronal Interactions during Oxidative Stress: Implications for Parkinson's Disease ..........................................................407 Catherine Mytilineou 24 • Astrocytic Changes Associated with Epileptic Seizures ........................421 Angélique Bordey and Harald Sontheimer 25 • Synaptic and Neuroglial Pathobiology in Acute and Chronic Neurological Disorders.............................................................................443 Lee J. Martin 26 • Astrocytes and Ammonia in Hepatic Encephalopathy ..........................477 Michael D. Norenberg Index ........................................................................................................................497