Table Of ContentNeuroglia in the Aging Brain
Contemporary Neuroscience
Pathogenesis of Neurodegenerative Disorders, Neurotransmitter Transporters: Structure,
edited by Mark P. Mattson, 2001 Function, and Regulation, edited by
Neurobiology of Spinal Cord Injury, edited Maarten E. A. Reith, 1997
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Strittmatter,2000 Research Issues and Applications,
Cerebral Signal Transduction: From First to edited byPaul R. Sanberg, Klaus-Peter
Fourth Messengers, edited by Maarten E. Ossenkopp,and Martin Kavaliers,
A. Reith, 2000 1996
Central Nervous System Diseases: Innovative Neurotherapeutics: Emerging Strategies,
Animal Models from Lab to Clinic, edited edited by Linda M. PullanandJitendra
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Dean, III, and Paul R. Sanberg,2000 Neuron–Glia Interrelations During
Mitochondrial Inhibitors and Neurodegen- Phylogeny: II. Plasticity
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Sanberg, Hitoo Nishino, and Cesario V. Vernadakis and Betty I. Roots, 1995
Borlongan,2000 Neuron–Glia Interrelations During
Cerebral Ischemia: Molecular and Cellular Phylogeny: I. Phylogeny
Pathophysiology, edited by Wolfgang and Ontogeny of Glial Cells, edited by
Walz, 1999 Antonia VernadakisandBetty I. Roots,
Cell Transplantation for Neurological Disor- 1995
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and Håkan Widner, 1998 Peptides,edited by William F. Colmers
Gene Therapy for Neurological Disorders andClaes Wahlestedt, 1993
and Brain Tumors, edited by E. Antonio Psychoactive Drugs: Tolerance and Sensiti-
Chiocca and Xandra O. Breakefield, zation,edited by A. J. GoudieandM. W.
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Highly Selective Neurotoxins: Basic and Experimental Psychopharmacology, edited
Clinical Applications, edited by Richard by Andrew J. Greenshaw and Colin T.
M. Kostrzewa, 1998 Dourish, 1987
Neuroinflammation: Mechanisms and Man- Developmental Neurobiology of the Auto-
agement,edited by Paul L. Wood, 1998 nomic Nervous System,edited by Phyllis
Neuroprotective Signal Transduction, edited M. Gootman, 1986
byMark P. Mattson, 1998 The Auditory Midbrain, edited by Lindsay
Clinical Pharmacology of Cerebral Ischemia, Aitkin, 1985
edited by Gert J. Ter Horst andJakob Neurobiology of the Trace Elements,edited by
Korf,1997 Ivor E. Dreosti and Richard M. Smith:
Molecular Mechanisms of Dementia, edited Vol. 1: Trace Element Neurobiology and
byWilma Wasco andRudolph E. Tanzi, Deficiencies,1983; Vol. 2: Neurotoxicology
1997 and Neuropharmacology, 1983
Neuroglia
in the
Aging Brain
Edited by
Jean S. de Vellis,
PhD
UCLA Mental Retardation Research Center,
Los Angeles, CA
Foreword by
Paola S. 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.
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do not necessarily reflect the views of the publisher.
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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
