Table Of ContentHANDBOOK OF NEUROTOXICOLOGY
SECTION EDITORS
David J. Adams
University of Queensland, St. Lucia, Australia
Daniel G. Baden
UNC Wilmington, Wilmington, NC
Jeffrey R. Bloomquist
Virginia Polytechnic Institute and State University, Blacksburg, VA
Marion Ehrich
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA
Tomas R. Guilarte
Johns Hopkins University, Baltimore, MD
Alan Harvey
University ofStrathclyde, Glasgow, UK
HANDBOOK
OF NEUROTOXICOLOGY
Volume I
Edited by
J.
EDWARD MASSARO
The National Health and Environmental Effects
Research Laboratory, Research Triangle Park,
Durham, NC
SPRINGER SCIENCE+BUSINESS
MEDIA,LLC
© 2002 Springer Science+Business Media New York
Originally published by Humana Press Inc in 2002
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Library of Congress Cataloging-in-Publication Data
Handbook of neurotoxicology I edited by Edward J. Massaro.
p. cm.
Includes bibliographical references and index.
ISBN 978-1-61737-193-6 ISBN 978-1-59259-132-9 (eBook)
DOI 10.10071978-1-59259-132-9
I. Neurotoxicology--Handbooks, manuals, etc. I. Massaro, Edward J.
RC347.5 .N4857 2001
616.8'047--dc21
2001039605
PREFACE
Neurotoxicology is a broad and burgeoning field of research. Its growth in recent years
can be related, in part, to increased interest in and concern with the fact that a growing
number of anthropogenic agents with neurotoxic potential, including pesticides, lead,
mercury, and the polytypic bypro ducts of combustion and industrial production, continue
to be spewed into and accumulate in the environment. In addition, there is great interest
in natural products, including toxins, as sources of therapeutic agents. Indeed, it is well
known that many natural toxins of broadly differing structure, produced or accumulated
for predatory or defensive purposes, and toxic agents, accumulated incidentally by
numerous species, function to perturb nervous tissue. Components of some of these
toxins have been shown to be useful therapeutic agents and/or research reagents. Unfor
tunately, the environmental accumulation of some neurotoxic ants of anthropogenic ori
gin, especially pesticides and metals, has resulted in incidents of human poisoning, some
of epidemic proportion, and high levels of morbidity and mortality. Furthermore, an
increasing incidence of neurobehavioral disorders, some with baffling symptoms, is
confronting clinicians. It is not clear whether this is merely the result of increased vigi
lance and/or improved diagnostics or a consequence of improved health care. In any case,
the role of exposure to environmental and occupational neurotoxic ants in the etiology of
these phenomena, as well as neurodegenerative diseases, is coming under increasing
scrutiny and investigation.
Recognition and utilization of environmental (in the broadest sense) information com
prise the currency of life. Therefore, the effects of perturbation of these critical capacities
deserve thorough investigation. The acquisition of information, and its processing, stor
age, retrieval, and integration leading to functional outputs, are fundamental nervous
system functions. It should not be surprising, then, that structural, functional, and evo
lutionary research has revealed that even "simple" nervous systems are immensely com
plex. On the systems level, the intact nervous system is an exquisite example of integration
within the context of a continuously evolving, apparently infinitely programmable and
regulatable hierarchical input/output system of complex chemical structure. However, as
the complexity of nervous systems has increased, so has their vulnerability to chemical
and physical insult. In part, this is a consequence of loss of regenerative capacity.
Living systems have evolved to function within relatively narrow ranges of environ
mental conditions. Perturbation beyond the limits of the range of a given system can result
in irreversible damage manifested as loss of function or viability. Also, the nervous tissue
of more highly evolved organisms is particularly refractory to regeneration. But, with
complexity has come an increased capacity for compensability. Albeit often limited and
difficult to achieve, through learning and recruitment, compensation can bypass irrevers
ible damage allowing, to varying degrees, recovery of function. The developing brain, in
particular, is endowed with immense plastic potential. Unfortunately, the efficiency of
both homeostatic and compensatory mechanisms progressively diminishes as a function
of aging. Indeed, a large body of literature indicates that humans generally lose memory
with age and the magnitude and rate of loss are highly variable among individuals. In
addition, data obtained through the medium of testing protocols, and supported by evi
dence obtained from functional neuroimaging studies, indicate that not all types of
v
vi Preface
memory are affected equally. Depending on the task, such studies show that, compared
with younger adults, older adults can display greater or lesser activity in task-associated
brain areas. Conceivably, the increases in activity may be the result of the input from
compensatory mechanisms. In any case, age-related diminished mental capacity is a
complex function of the interaction of genetic constitution and environmental factors.
The type, magnitude, duration, and period of exposure in the life cycle to the latter can
impact the functional status of the aging nervous system. Major windows of vulnerability
occur during development, when target sizes are small and defense mechanisms imma
ture, and in post-maturity, following decline of the functioning of compensatory and
defense mechanisms along with increased duration of exposure.
Intellectually, we may appreciate that thermodynamics dictates that, as a function of
population size, environmental pollution will increase. However, do we appreciate that,
in the short-run, if a connection between environmental pollution and nervous system
damage exists, the incidence of nervous system damage will increase as the population
increases? Likewise, as life span increases, exposure to neurotoxic ants will increase and,
it is not unreasonable, therefore, to predict that the incidence of neurodegenerative dis
eases also will increase. Are these phenomena self-limiting? If not, can we estimate the
magnitude of these problems that ensuing generations will have to face? With time,
sufficient funding, and manpower, it may be possible to solve many of these problems.
Indeed, we must. If not, the consequences border on the Orwellian.
With an eye to the future, the Handbook of Neurotoxicology has been developed to
provide researchers and students with a view of the current status of research in selected
areas of neurotoxicology and to stimulate research in the field. Obviously, the field is
enormous and all areas of interest could not be covered. However, if the Handbook of
Neurotoxicology, volumes 1 and 2 prove useful, other volumes will be forthcoming.
Therefore, we invite your comments and suggestions.
Edward J. Massaro
CONTENTS
Preface ............................................................................................................................ v
Companion Table of Contents ...................................................................................... xi
Contributors ................................................................................................................ xiii
I. PESTICIDES
Marion Ehrich and Jeffrey R. Bloomquist, Section Editors
A. Anticholinesterase Insecticides
1 Acute Toxicities of Organophosphates and Carbamates ................. 3
Janice E. Chambers and Russell L. Carr
2 Organophosphate-Induced Delayed Neuropathy ........................... 17
Marion Ehrich and Bernard S. Jortner
3 Nonesterase Actions of Anticholinesterase Insecticides ............... 29
Carey Pope and Jing Liu
B. Pesticides that Target Ion Channels
4 Agents Affecting Sodium Channels ............................................... 47
David M. Soderlund
5 Agents Affecting Chloride Channels ............................................. 65
Jeffrey R. Bloomquist
6 The Neonicotinoid Insecticides ...................................................... 79
Larry P. Sheets
C. Miscellaneous Pesticides with Action on the Nervous System
7 Miscellaneous Pesticides with Action on the Nervous System ..... 91
Dennis Blodgett, Marion Ehrich, and Jeffrey R. Bloomquist
II. METALS
Tomas R. Guilarte, Section Editor
8 Molecular Mechanisms of Low-Level Pb2+ Neurotoxicity ......... 107
Michelle K. Nihei and Tomas R. Guilarte
9 Elucidation of the Zinc-Finger Motif as a Target for Heavy-Metal
Perturbations .............................................................................. 135
Nasser H. Zawia and Morad Razmiafshari
10 Blood-Brain Barrier and Blood-CSF Barrier in Metal-Induced
Neurotoxicities .......................................................................... 161
WeiZheng
11 Manganese in Health and Disease: From Transport to Neurotoxicity .. 195
Michael Aschner, James R. Connor, David C. Dorman,
Elise A. Malecki, and Kent E. Vrana
vii
viii Contents
12 Aluminum Neurotoxicity .............................................................. 211
Andrzej Szutowicz
III. NATURAL TOXINS OF MICROBIAL ORIGIN
David J. Adams and Daniel G. Baden, Section Editors
13 Ecology of Microbial Neurotoxins ............................................... 239
Lyndon E. Llewellyn
14 Biosynthesis of Important Marine Toxins of Microorganism
Origins ....................................................................................... 257
Yuzuru Shimizu
15 Biological Assay and Detection Methods for Marine
"Shellfish" Toxins ................................................................... 269
Neale R. Towers and Ian Garthwaite
16 An Overview of Clostridial Neurotoxins ..................................... 293
Mark A. Poli and Frank J. Lebeda
17 Molecular Mechanism of Action of Botulinal Neurotoxins
and the Synaptic Remodeling They Induce In Vivo
at the Skeletal Neuromuscular Junction ................................... 305
Frederic A. Meunier, Judit Herreros, Giampietro Schiavo,
Bernard Poulain, and Jordi Molgo
18 Marine Mammals as Sentinels of Environmental Biotoxins ....... 349
Vera L. Trainer
19 The Epidemiology of Human Illnesses Associated with Harmful
Algal Blooms ............................................................................ 363
Lora E. Fleming, Lorraine Backer, and Alan Rowan
IV.
NATURAL TOXINS OF ANIMAL ORIGIN
Alan Harvey, Section Editor
20 Snake Neurotoxins that Interact with Nicotinic Acetylcholine
Receptors .................................................................................. 385
Denis Servent and Andre Menez
21 Presynaptic Phospholipase A2 Neurotoxins from Snake
Venoms ..................................................................................... 427
John B. Harris
22 Dendrotoxins from Mamba Snakes .............................................. 455
J. Oliver Dolly and Giacinto Bagetta
23 Neurotoxins from Spider Venoms ............................................... .475
Alfonsi'J Grasso and Stefano Rufini
24 Neurotoxins from Scorpion Venoms ............................................ 503
Marie-France Martin-Eauclaire
25 Anthozoan Neurotoxins ................................................................ 529
William R. Kem
Contents ix
26 Nemertine Neurotoxins ................................................................. 573
William R. Kem
27 Secretagogue Activity of Trachynilysin, a Neurotoxic Protein
Isolated from Stonefish (Synanceia trachynis) Venom ........... 595
Frederic A. Meunier, Gilles Ouanounou, Cesar Mattei,
Pascal Chameau, Cesare Colasante, Yuri A. Ushkaryov,
l. Oliver Dolly, Arnold S. Kreger, and lordi Molgo
28 Neurotoxins of Cone Snail Venoms ............................................. 617
Robert Newcomb and George Miljanich
Index ........................................................................................................................... 653
CONTENTS OF THE COMPANION VOLUME
Handbook of Neurotoxicology
Volume II
I. DEVELOPMENTAL NEUROTOXICOLOGY
James L. Schardein, Section Editor
1 Interpretation of Developmental Neurotoxicity Data
Judith W. Henck
2 Manifestations of CNS Insult During Development
Susan A. Rice
3 Developmental Neurotoxicology: What Have We Learned
from Guideline Studies?
Gregg D. Cappon and Donald D. Stump
4 Risk Assessment of Developmental Neurotoxicants
Hugh A. Tilson
II. DRUGS OF ABUSE
Patricia A. Broderick, Section Editor
5 Electrophysiologic Evidence of Neural Injury or Adaptation
in Cocaine Dependence
Kenneth R. Alper, Leslie S. Prichep, E. Roy John,
Sharon C. Kowalik, and Mitchell S. Rosenthal
6 Addictive Basis of Marijuana and Cannabinoids
Eliot L. Gardner
7 Dopamine and Its Modulation of Drug-Induced Neuronal
Damage
Donald M. Kuhn
8 NMDA Antagonist-Induced Neurotoxicity and Psychosis:
The Dissociative Stimulation Hypothesis
Kevin Kiyoshi Noguchi
9 Emerging Drugs of Abuse: Use Patterns and Clinical Toxicity
Katherine R. Bonson and Matthew Baggott
10 Mechanisms of Methamphetamine-Induced Neurotoxicity
Jean Lud Cadet and Christie Brannock
11 Neurotoxic Effects of Substituted Amphetamines in Rats
and Mice: Challenges to the Current Dogma
James P. O'Caliaghan and Diane B. Miller
xi
