HANDBOOK 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 Softcover reprint of the hardcover 1s t edition 2002 All rights reserved. No part of this book may be rcproduced, 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. Tbe content and opinions expressed in this book are the sole work of the authors and editors, who have warranted due diligence in the creation and issuance of their work. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences arising from the information or opinions presented in this book and make no warranty, express or implied, with respect to its contents. Cover illustration: Figure 2B from Chapter 2, "Organophosphate-Induced Delayed Neuropathy," by Marion Ehrich and Bernard S. Jortner. Production Editor: Jessica Jannicelli. Cover design by Patricia F. Cleary. 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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. 10987654321 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