Cerebral Signal Transduction: From First to Fourth Messengers

422 Pages·2000·9.012 MB·English

by  Maarten E. A. Reith (auth.), Maarten E. A. Reith (eds.)

Cerebral Signal Transduction
Contemporary Neuroscience
Cerebral Signal Transduction: From Neurotransmitter Transporters: Struc
First to Fourth Messengers, edited ture, Function, and Regulation,
by Maarten E. A. Reith, 2000 edited by Maarten E. A. Reith,
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Innovative Animal Models from Lab Motor Activity and Movement Disor
to Clinic, edited by Dwaine F. ders: Research Issues and Applica
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and Paul R. Sanberg, 2000 edited by Paul R. Sanberg,
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and Cesario V. Borlongan, 2000 gies, edited by Linda M. Pullan
Cerebral Ischemia: Molecular and and Jitendra Patel, 1996
Cellular Pathophysiology, edited Neuron-Glia Interrelations During
by Wolfgang Walz, 1999 Phylogeny: II. Plasticity
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Disorders, edited by Thomas B. Antonia Vernadakis and Betty I.
Freeman and Hakan Roots, 1995
Widner,1998 Neuron-Glia Interrelations During
Gene Therapy for Neurological Disor Phylogeny: I. Phylogeny
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Claes Wahlestedt, 1993
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Molecular Mechanisms of Dementia,
edited by Wilma Wasco and
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Cerebral Signal
Transduction
From First to Fourth Messengers
Edited by
Maarten E. A. Reith
of of
College Medicine, University Illinois, Peoria, IL
~
Humana Press
~
Totowa, New Jersey
© 2000 Humana Press Inc.
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Library of Congress Catalog ing in Publication Data
Cerebral signal transduction : from first to fourth messengers / edited by Maarten E. A. Reith.
p. cm. --(Contemporary neuroscience)
Includes bibliographical references and index.
ISBN 978-1-4684-9615-4 ISBN 978-1-59259-019-3 (eBook)
DOI 10.1007/978-1-59259-019-3
1. Molecular neurobiology. 2. Cellular signal transduction.
3. Nervous system--Diseases--Molecular aspects. 4. Nervous system
Degeneration--Molecular aspects. 5. Second messengers
(Biochemistryl I. Series.
[DNLM: 1. Signal Transduction--physiology. 2. Apoptosis
-physiology. 3. Depressive Disorder--physiopathology. 4. Memory-
-physiology. 5. Nerve Degeneration--physiopathology. 6. Signal
Transduction--drug effects. QH 601 C4139 2000]
QP356.2.C475 2000
612.8--dc21
DNLM/DLC 99-38476
for Library of Congress CIP
Preface
Since the pioneering discovery of cyclic AMP four decades ago, a
multitude of signaling pathways have been uncovered in which an
extracellular signal (first messenger) impacts the cell surface, thereby
triggering a cascade that ultimately acts on the cell nucleus. In each
cascade the first messenger gives rise to the appearance of a second
messenger such as cyclic AMP, cyclic GMP, or diacylglycerol, which in
turn triggers a third messenger, a fourth messenger, and so forth. Many
advances in elucidating such pathways have been made, including
efforts to link messenger molecules to brain processes operative in
health or disease. However, the latter type of information, relating
signaling pathways to brain function, is scattered across a variety of
publication media, which makes it difficult to integrate the multiple
roles of different signaling cascades into our understanding of brain
function in health and disease.
The primary aim of Cerebral Signal Transduction: From First to Fourth
Messengers, therefore, is to offer a comprehensive picture of the recent
advances made in the signaling field as it relates to neuronal and cere
bral function. The current state of progress provides an exciting
opportunity for such a comprehensive focus because molecular tools
have become available to selectively remove, reduce, or enhance spe
cific components in the signaling pathways, e.g., by interfering with
the genes encoding key proteins. In addition, the increased awareness
of crosstalk between different signaling cascades has revealed many
possibilities for changes in gene expression underlying long-term
changes in brain function.
Normal cerebral functions, such as memory or apoptosis during
development, may be compromised in disease, as seen in Alzheimer's,
in such neurodegenerative diseases as Parkinson's, Huntington's, or
amyotrophic lateral sclerosis, or in stroke and brain trauma. In addi
tion, there has been recent progress in elucidating the role of signaling
messengers in depression and in the action of drugs of abuse. Accord
ingly, Cerebral Signal Transduction: From First to Fourth Messengers is
organized around four themes involving brain functions: memory,
v
Preface
VI
neurodegeneration/ apoptosis, mood disorders, and drug depen
dence. This book advances understanding of the mechanistic under
pinnings for complex behavioral processes and clinically relevant brain
diseases, and will be of interest to scientists, graduate students, and
advanced undergraduates seeking a comprehensive overview of the
cerebral signaling field. Selected chapters will also be of interest to
physicians carrying out postmortem measurements related to cerebral
signaling and who wish to study in more detail the mechanisms under
lying brain diseases and the actions of pharmacotherapeutics. Most
therapeutic drugs target the effect of first messengers (neurotransmit
ters) by either interfering with or mimicking their receptor action or
altering their levels by acting on enzymes involved in their synthesis,
degradation, or storage. The future will undoubtedly see new drugs
targeting events downstream in the cascade of second, third, and fourth
messengers, and we believe that Cerebral Signal Transduction: From First
to Fourth Messengers will contribute to progress towards such novel
pharmacotherapeutics.
Each chapter in Cerebral Signal Transduction: From First to Fourth Mes
sengers is not simply a review of the work carried out in the author's
laboratory, but rather presents a critical survey and synthesis of achieve
ments in that area. Chapter 1 offers an overview of the various signaling
cascades and their crosstalk, with the intent to provide basic resource
material for reading the more specialized subsequent chapters. Under
the section Memory, Chapters 2-4 discuss cAMP /PKA, Ca2+ /
calmodulin-dependent protein kinase, DAG/PKC, and NO/PKG sig
naling pathways operative in learning and memory. The coverage
includes simpler model systems for learning and memory such asAplysia
californica (Chap. 2) and Drosophila (Chap. 3) as well as more complicated
systems including the honeybee (Chap. 3) and the mammalian hippo
campus (Chaps. 2 and 4). Under the section Neurodegeneration and
Apoptosis, Chaps. 5-8 describe cAMP /PKA, DAG/PKC, NO /PKG, and
neurotrophic factor signaling cascades involved in these processes.
Chapter 5 focuses on receptor-G protein interactions in Alzheimer's
disease and Chap. 6 on NO signaling involved in neural injury, neuro
logical disorders, and aggression. Chapter 7 discusses pro- and anti
apoptotic neurotrophic factor signaling pathways involving Ras, and
Chap. 8 focuses on pathways in neurodegeneration that utilize Ca2+.
Both Chaps. 5 and 8 connect signaling messengers in neurodegenera
tion with clinical findings in or implications for humans. Under the
section Depression, Chaps. 9-11 cover cAMP /PKA, DAG/PKC, and
Preface
Vll
neurotrophic factor signaling pathways thought to be important in the
development and treatment of mood disorders. Stress and the devel
opment of depression are linked through cAMP jPKA (Chap. 9) and
neurotrophic factor pathways (Chaps. 9 and 10) potentially involved
in the novel, nonconvulsive treatment of repeated trans cranial mag
netic stimulation (Chap. 10). A strong connection between signaling
messengers in mood disorders and clinical findings is continued in
Chap. 11 focusing on components of the cAMP jPKA and DAGjPKC
cascades. In the section Drug Dependence, Chaps. 12-15 discuss DAG j
PKC signaling pathways and other cascades regulating the production
of transcription factors implicated in the development and expression
of drug dependence. Various signaling pathways in opiate (Chap. 12)
and psychostimulant (Chaps. 13-15) dependence are discussed
involving cyclic AMP, protein kinases, and transcription factors. Chap
ters 12 and 13 review the wealth of information that has come from
recent studies with knockout mice lacking genes for the production of
various key signaling messengers or receptor proteins acted upon by
messengers. Chapters 14 and 15 discuss the role of the dopamine
transporter in regulating the first messenger dopamine involved in the
action of psychostimulant drugs, in particular that of cocaine. Phos
phorylation of the dopamine transporter by the DAGjPKC signaling
pathway is described (Chap. 14) and the transcriptional regulation of
the dopamine transporter is reviewed (Chap. 15). Additionally, the
latter chapter links pharmacodynamic mechanisms operative in
human cocaine dependence with those studied in animal models.
The choice of authors for each chapter reflects the editor's identifi
cation of investigators who have been instrumental in developing these
new frontiers in neuroscience. I thank the authors for their patience,
during the process of putting this book together. I deeply appreciate
the opportunity offered by Paul Dolgert and Tom Lanigan at Humana
Press to produce this book in recognition of the importance of cerebral
signal transduction in both health and disease.
Maarten E. A. Reith
Contents
Preface ......................................................................................................... v
Contributors .............................................................................................. xi
PART I. INTRODUCTION
1 • From First to Fourth Messengers in the Brain:
An Overview .................................................................................. 3
Maarten E. A. Reith
PART II. MEMORY
2 • Cellular and Molecular Mechanisms of Learning
and Memory ................................................................................ 27
Matthew Lattal and Ted Abel
3 • Signal Transduction Pathways in Well-Defined
Models of Learning and Memory: Drosophila
and Honeybee ................................................................................ 73
Uli Milller
4 • Protein Kinase C Signaling in Learning
and Memory .............................................................................. 105
Eddy A. Van der Zee, Bas R. K. Douma,
John F. Disterhoft, and Paul G. M. Luiten
PART III. NEURODEGENERATION AND ApOPTOSIS
5 • Neurotransmitter Receptor-G-Protein-Mediated
Signal Transduction in Alzheimer's Disease ...................... 129
Richard F. Cowburn
6 • The NO Signaling Pathway in the Brain: Neural
Injury, Neurological Disorders, and Aggression .................... 151
Masayuki Sasaki, Va lin a L. Dawson, and Ted M. Dawson
ix
x Contents
7 • Cellular Signaling Pathways in Neuronal Apoptosis:
Role in Neurodegeneration and Alzheimer's Disease ............... 175
Carl W. Cotman, Haoyu Qian, and Aileen J. Anderson
8 • The Role of Second Messengers in Neurodegeneration ....... 207
Aase Frandsen, Jette Bisgaard Jensen, and Arne Schousboe
P ART IV. DEPRESSION
9 • Molecular and Cellular Determinants of Stress
and Antidepressant Treatment ............................................. 223
Ronald S. Duman
10 • Long-Term Bidirectional Hormonal and Neuroplastic
Responses to Stress: Implications for the Treatment
of Depression ............................................................................... 249
Robert M. Post, Susan R. B. Weiss, Li-Xin Zhang,
and M. Guoqiang Xing
11 • Signal Transduction Abnormalities in Bipolar
Affective Disorder ................................................................... 283
Peter P. Li, Stavroula Andreopoulos, and Jerry J. Warsh
PART V. DRUG DEPENDENCE
12 • Messengers in Opioid Dependence: Gene
Disruption Studies ..................................................................... 313
Rafael Maldonado and Olga Valverde
13 • The 5-HT1B Knockout Mouse: An Animal Model
of Vulnerability to Drugs of Abuse ........................................... 341
Kimberly Scearce-Levie and Rene Hen
14 • Regulation of Dopamine Transporter by Phosphorylation
and Impact on Cocaine Action .............................................. 375
Roxanne A. Vaughan
15 • Dopamine Transporter mRNA in Human Brain:
Distribution and Regulatory Effects in Autopsy Studies
of Cocaine Abusers ..................................................................... 401
Deborah C. Mash, Li Chen Kramer, David Segal,
and Sari Izenwasser
Index ........................................................................................................ 419
Contributors
TED ABEL· Department of Biology, University of Pennsylvania,
Philadelphia, P A
AILEEN J. ANDERSON· Institute for Brain Aging and Dementia, University
of California, Irvine, CA
STA VROULA ANDREOPOULOS • Section of Biochemical Psychiatry, Clarke
Division, Center for Addiction and Mental Health, Toronto, Canada
CARL W. COTMAN • Institute for Brain Aging and Dementia, University
of California, Irvine, CA
RICHARD F. COWBURN· Department of Clinical Neuroscience, Occupational
Therapy and Elderly Care Research (NEUROTEC), Alzheimer's Disease
Resesarch Center, Karolinska Institute, Huddinge, Sweden
TED M. DAWSON • Departments of Neurology and Neuroscience, John
Hopkins University School of Medicine, Baltimore, MD
VALINA L. DAWSON· Departments of Neurology, Neuroscience, and Physiology,
John Hopkins University School of Medicine, Baltimore, MD
JOHN F. DISTERHOFT • Department of Cell and Molecular Biology,
Northwestern University Medical School, Chicago, IL
BAS R. K. DOUMA • Department of Animal Physiology, University
of Groningen, Haren, The Netherlands
RONALD S. DUMAN • Departments of Psychiatry and Pharmacology, Yale
University School of Medicine, New Haven, CT
AASE FRANDSEN • Department Pharmacology, Royal Danish School of
Pharmacy, Copenhagen, Denmark
RENE HEN· Center for Neurobiology and Behavior, Columbia University,
New York, NY
SARI IZENWASSER· Department of Neurology, University of Miami School
of Medicine, Miami, FL
JETTE BISGAARD JENSEN • Department of Pharmacology, Royal Danish
School of Pharmacy, Copenhagen, Denmark
LI CHEN KRAMER· Department of Neurology, University of Miami School
of Medicine, Miami, FL
MATTHEW LATTAL • Department of Biology, University of Pennsylvania,
Philadelphia, P A
xi