Table Of ContentMicroglia in the Regenerating and
Degenerating Central Nervous System
Springer Science+Business Media, LLC
Wolfgang J. Streit
Editor
Microglia in the Regenerating
and Degenerating Central
Nervous System
With 44 Illustrations
, Springer
Wolfgang J. Streit
Department of Neuroscience
University of Florida College of Medicine
100 Newell Drive
Gainesville, FL 32611
USA
[email protected]
Library of Congress Cataloging-in-Publieation Data
Mieroglia in the regenerating and degenerating eentral nervous system / [edited by 1
Wolfgang 1. Streit
p. em.
Inc1udes bibliographical references and index.
1. Nervous system-Degeneration. 2. Nervous system-Regeneration. 3. Microglia.
I. Streit, WJ. (Wolfgang J.)
RC365.M53 2001
616.8'047-dc21 2001032813
ISBN 978-1-4419-2944-0 ISBN 978-1-4757-4139-1 (eBook)
DOI 10.1007/978-1-4757-4139-1
Printed on aeid-free paper.
© 2002 Springer Science+Business Media New York
Originally published by Springer-Verlag New York,Inc in 2002.
Softcover reprint of the hardcover 1s t edition 2002
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Preface
This book is focused on the functions of microglial ceHs during neuronal regener
ation and degeneration. Regeneration and degeneration in the Central Nervous
System (CNS) are influenced profoundly by the activities of microglia, and
neuron-microglia interactions are increasingly becoming the subject of intense re
search activity, Elucidating the molecular mechanisms of neuron-microglia inter
actions is of vital interest for understanding the consequences of acute traumaticl
ischemic injury, as weH as the pathogenesis of chronic neurodegenerative pro
cesses, in particular Alzheimer's disease (AD). This book is meant to provide an
up-to-date summary of microglial ceH function and their relevance to these acute
and chronic pathological states.
So what's new with microglia? We have leamed a lot about normal physiolog
ical functions of microglia from studying their activities in CNS pathology. The
general concept that emerges is that microglia have a role in determining neuronal
survival and death and that their primary role in the normal CNS is to support and
protect neuron vi ability. Microglia are our neurons' friends. They have been
called "sentineIs" and "sensors of pathology," terms that underscore this physio
logical function. However, what would happen if microglia ceased to function
properly and became pathological? This book introduces the idea of microglial
dysfunction as a pathological mechanism for neurodegenerative disease. In addi
tion, the chapters in this book address a spectrum of novel issues related to CNS
development, aging, Alzheimer's disease, as weH as to acute CNS injury and to
the molecular mechanisms of inter- and intracellular signaling.
What are the challenges for microglial research in the future? To refine the def
inition of various microglial activation states is one challenge, since there are
many different levels of microglial activation. To define the molecular and genetic
changes that occur in microglia with aging will become increasingly important as
the incidence of Alzheimer's disease continues to grow. To investigate how mi
croglia remodel synaptic connections and how they guide axons during develop
ment or during post-injury repair will be important for deve10ping strategies to re
pair the injured spinal cord. To identify the molecular nature of neuronal signals
that control microglial activity will be useful for leaming to manipulate microglial
function as part of the treatment of injury and disease. To identify how systemic
v
VI Preface
disease affects microglia will remind us neuroscientists that the brain is but one
organ in the organism. The list goes on.
I want to express my appreciation to all contributing authors, some of whom are
former students, some are colleagues, some are friends, and some are all of the
above. It is gratifying to see how everybody's part helped shape the final product.
Without them this book would not have been written.
University of Florida Wolfgang J. Streit
Gainesville, Florida June 2000
Contents
Preface........................................................................................................... v
Contributors................ ......... ....... ................................... ....... ....... .... ....... ... .... ix
1. Physiology and Pathophysiology of Microglial Cell Function . ....... .... 1
Wolfgang l. Streit
2. Roles of Microglia in the Developing Avian Visual System ................ 15
luZio Navascues, MigueZ A., Cuadros, Ruth CaZvente,
and lose L. Marfn-Teva
3. Microglial Ion Channels ....................................................................... 36
CZaudia Eder
4. Calcium Signaling in Microglial Cells ................................................. 58
Thomas Möller
5. Microglia as a Source and Target of
Cytokine Activities in the Brain ......... ......... ........ ....... .................. ........ 79
Uwe-Karsten Hanisch
6. Microglia and Macrophage Responses in Cerebral Ischemia .............. 125
Guido StolI, Sebastian landeT, and Michael Schroeter
7. Role of Microglia and Macrophages in Secondary Injury
of the Traumatized Spinal Cord: Troublemakers or Scapegoats? ........ 152
Phillip G. Popovich
8. Microglial Response in the Axotomized Facial Motor Nucleus .......... 166
Gennadij Raivich
9. Neuroprotective Roles of Microglia in the Central Nervous System... 188
Kazuyuki Nakajima and Shinichi Kohsaka
Vll
V1ll Contents
10. Infiuences of Activated MicrogliaJBrain Macrophages
on Spinal Cord Injury and Regeneration.............................................. 209
Alexander G. Rabchevsky
11. Opportunities for Axon Repair in the CNS: U se of Microglia
and Biopolymer Compositions ............................................................. 227
Joshua B. Stopek, Wolfgang J. Streit, and Eugene P. Goldberg
12. Beta Amyloid Protein Clearance and Microglial Activation ................ 245
Sally A. Frautschy, Greg M. Cole, and March D. Ard
13. Microglia andAging in the Brain......................................................... 275
Caleb E. Finch, Todd E. Morgan, Irina Rozovsky, Zhong Xie,
Richard Weindruch, and Tomas Prolla
Index.............................................................................................................. 307
Contributors
March D. Ard, Ph.D., Department of Anatomy, University ofMississippi Medical
Center, 2500 N. State St., Jackson, MS 39216, USA
Ruth Calvente, Ph.D., Departamento de Biologfa Celular, Facultad de Ciencias,
Universidad de Granada, E-18071, Granada, Spain
Greg M. Cole, Ph.D., UCLA, Departments of Medicine and Neurology, Greater
Los Angeles Healthcare System, VA Medical Center 16111 Plummer St., Sepul
veda, CA 91343, USA
Miguel A. Cuadros, Ph.D., Departamento de Biologfa Celular, Facultad de Cien
cias, Universidad de Granada, E-18071, Granada, Spain
Claudia Eder, Ph.D., Abteilung Neurophysiologie Insitut für Physiologie der Char
ite, Humboldt Universitaet zu Berlin, Tucholskystr. 2, D-lO 117, Berlin Germany
[email protected]
Caleb E. Finch, Ph.D., Andrus Gerontology Center, School of Gerontology and
Department of Biological Sciences, University of Southem Califomia, Los Ange
les, CA 90089-0191, USA
[email protected]
Sally A. Frautschy, Ph.D., UCLA, Departments of Medicine and Neurology,
Greater Los Angeles Healthcare System, VA Medical Center, 16111 P1ummer St.,
Sepulveda, CA 91343, USA
[email protected]
Eugene P. Goldberg, Ph.D., Biomaterials Center, Department ofMaterial Science
and Engineering, P.O. Box 116400, RM. 239 MAE, University of Florida College
of Engineering, Gainesville, FL 32611, USA
Sebastian lander, M.D., Department of Neurology, Heinrich-Heine Universität,
Düsseldorf, Moorenstr. 5, 40255 Düsseldorf, Germany
Shinichi Kohsaka, Ph.D., M.D., Department ofNeurochemistry, National Institute
of Neuroscience, 4 -1-1 Ogamahigashi, Kodaira Tokyo, 187-8502
[email protected]
ix
x Contributors
lose L. Marfn-Teva, Ph.D., INSERM, U.495 Höpital de la Salpetriere, 47 Boule
vard de l'Höpital, F-75651 Paris (Cedex 13), France
[email protected]
Thomas Möller, Ph.D., Department of Neurology, University of Washington, De
partment of Neurology, Box 356465. 1959 NE Pacific Street, Seattle, WA 98195,
USA
[email protected]
Todd E. Morgan, Ph.D., Andrus Gerontology Center, School of Gerontology, Uni
versity of Southem Califomia, Los Angeles, CA 90089-0191, USA
[email protected]
Kazuyuki Nakajima, Ph.D., Institute of Life Science, Soka University 1-236
Tangi-machi, Hachioji, Tokyo 192-8577
[email protected]
lulio Navascues, Ph.D., Departamento de Biologfa Celular, Facultad de Ciencias,
Universidad de Granada, E-18071, Granada, Spain
[email protected]
Phillip G. Popovich, Ph.D., The Ohio State University College of Medicine and
Public Health, Department of Molecular Virology, Immunology and Medical Ge
netics, 333 W. 10th Avenue, 2078 Graves Hall, Columbus, OH 43210, USA
[email protected]
Tomas Prolla, Ph.D., Department of Medical Genetics, University ofWisconsin,
Madison, WI 53706, USA
Alexander G. Rabchevsky, Ph.D., 229 Sanders-Brown Center on Aging, Univer
sity of Kentucky, Lexington, KY 40536-0230, USA
[email protected]
Gennadij Raivich, Ph.D., M.D., Perinatal Brain Repair Group, Department of Ob
stetrics and Gynecology, Department of Anatomy, University College London,
Gower Street Campus 86-96 Chenies Mews, London wcm 6HX, UK.
[email protected] and [email protected]
Irina Rozovsky, Ph.D., Andrus Gerontology Center, School of Gerontology, Uni
versity of Southem Califomia, Los Angeles, CA 90089-0191, USA
[email protected]
Michael Schroeter, M.D., Department of Neurology, Heinrich-Heine Universität,
Düsseldorf, Moorenstr. 5,40255 Düsseldorf, Germany
Guido StolI, M.D., Professor of Neurology, Department of Neurology, Julius
Maximilians-Universität Würzburg, Josef-Schneider Str. 11, 97080 Würzburg
Germany
[email protected]_wuerzburg.de
