Molecular Neurosurgery With Targeted Toxins PDF
Preview Molecular Neurosurgery With Targeted Toxins
MOLECULAR NEUROSURGERY WITH TARGETED TOXINS MOLECULAR NEUROSURGERY WITH TARGETED TOXINS Edited by RONALD G. WILEY, MD, PhD Departments of Neurology and Pharmacology, Vanderbilt University School of Medicine and Neurology Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN and DOUGLAS A. LAPPI, PhD Advanced Targeting Systems, San Diego, CA © 2005 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 humanapress.com 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. All papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. The 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 infor- mation or opinions presented in this book and make no warranty, express or implied, with respect to its contents. Production Editor: Amy Thau Cover Illustration: Cover design by Patricia F. Cleary. For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341; E-mail: PREFACE The use of targeted cytotoxins in experimental neurobiology is a new field. This strategy involves producing highly selective neural lesions by targeting a cytotoxin into specific neurons based on their binding to surface membrane targets, such as neurotransmitter or growth factor receptors, and so on. The goal is to produce lesions of unprecedented selectivity to match the staggering complexity of the organization of the nervous system. Indeed, a considerable body of evidence exists that the expression of surface membrane molecules correlates with the function of specific types of neurons. Molecular Neurosurgery With Targeted Toxins seeks to provide a selected collection of examples of this approach that have been implemented with great success. Included are introductory considerations and background on the toxins, followed by five chapters reviewing the use of the immunotoxin 192 IgG-saporin to lesion the cholinergic basal forebrain. This approach has been highly successful, and as pointed out by the authors, has provided a valuable animal model of Alzheimer’s disease. However, it is hardly the only application of targeted toxins in neuroscience. Subsequent chapters include reviews of some of the varied uses of another immunotoxin, anti-DBH-saporin, which is used to make remarkably selective lesions of catecholaminergic neurons, and a chapter on hypocretin–saporin that can be used to produce narcoleptic animals. A variety of other saporin conjugates, such as neuropeptide–saporin conjugates, are proving valuable in pain research; these are reviewed in two chapters, followed by a chapter on the novel application of cholera toxin B chain-saporin to produce a model of CNS demyelina- tion. The chapter authors were asked to provide both overview perspectives and, in some cases, more practical details to enable the reader to appreciate exactly what is involved in using these agents. We, the editors, have been intimately involved in the development of the agents discussed in this volume and present this body of information as an introduction to those who would use this approach in their own experiments. Ronald G. Wiley, MD, PhD Douglas A. Lappi, PhD v CONTENTS Preface ..................................................................................................................... v Contributors .......................................................................................................... ix 1 Introduction to Molecular Neurosurgery ...............................................1 Ronald G. Wiley and Douglas A. Lappi 2 Ribosome-Inactivating Proteins ...............................................................9 Fiorenzo Stirpe 3 Biochemical, Physiological, and Behavioral Characterizations of the Cholinergic Basal Forebrain Lesion Produced by 192 IgG-Saporin ............................................................................. 31 Jerene J. Waite 4 Basal Forebrain Cholinergic Lesion by 192 IgG-Saporin: A Tool to Assess the Consequences of Cortical Cholinergic Dysfunction in Alzheimer´s Disease .......................................................................... 59 Reinhard Schliebs 5 192 IgG-Saporin-Induced Partial Cortical Cholinergic Deafferentation as a Model for Determining the Interactions Between Brain Aging and Neurodevelopmental Defects in the Cortical Cholinergic Input System ....................................... 87 Martin Sarter and John P. Bruno 6 Exploring the Role of Acetylcholine in Primate Cognition Using Me20.4 IgG-Saporin .......................................................................... 101 Rosalind M. Ridley and Harry F. Baker 7 Cortical Cholinergic Deafferentation Induces AG Deposition: Toward a Physiological Animal Model of Alzheimer’s Disease ........ 143 Thomas G. Beach, D. G. Walker, P. E. Potter, L. I. Sue, S. Scott, K. J. Layne, A. J. Newell, P. K. Rauschkolb, M. E. Poston, S. D. Webster, R. A. Durham, M. R. Emmerling, K. Sawada, W. G. Honer, A. Fisher, and A. E. Roher 8 Chemical Dissection of Brain Glucoregulatory Circuitry .............. 181 Sue Ritter, Thu T. Dinh, Kishor Bugarith, and Dawna M. Salter 9 Cardiovascular Deficits After Lesions of C1 Adrenergic Neurons With a Saporin-Based Immunotoxin ............................ 219 Patrice G. Guyenet, Ruth L. Stornetta, and Ann M. Schreihofer vii viii Contents 10 Saporin Conjugates and Pain ............................................................... 235 Ronald G. Wiley and Douglas A. Lappi 11 The Use of Saporin Conjugates to Dissect Neurons Responsible for Sleep and Wakefulness ....................................... 249 Carlos Blanco-Centurion, Dmitry Gerashchenko, Eric Murillo-Rodriguez, Frank Desarnaud, and Priyattam J. Shiromani 12 Isolectin B4-Mediated Cytotoxic Targeting of Sensory Neurons ..... 265 Lucy Vulchanova and Christopher N. Honda 13 B Fragment of Cholera Toxin Conjugated to Saporin ..................... 293 Peter T. Ohara, Kanwarjit Kelley, and Luc Jasmin Index .................................................................................................................... 307 CONTRIBUTORS HARRY F. BAKER • Department of Experimental Psychology, School of Veterinary Medicine, Cambridge, UK THOMAS G. BEACH • Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, AZ CARLOS BLANCO-CENTURION • Department of Neurology, Harvard Medical School and Veterans Administration Medical Center, West Roxbury, MA JOHN P. BRUNO • Department of Psychology, Ohio State University, Columbus, OH KISHOR BUGARITH • Programs in Neuroscience, Washington State University, Pullman, WA FRANK DESARNAUD • Department of Neurology, Harvard Medical School and Veterans Administration Medical Center, West Roxbury, MA THU T. DINH • Programs in Neuroscience, Washington State University, Pullman, WA R. A. DURHAM • Pfizer Pharmaceuticals, Ann Arbor, MI M. R. EMMERLING • Pfizer Pharmaceuticals, Ann Arbor, MI A. FISHER • Israel Institute for Biological Research, New Ziona, Israel DMITRY GERASHCHENKO • Department of Neurology, Harvard Medical School and Veterans Administration Medical Center, West Roxbury, MA PATRICE G. GUYENET • Department of Pharmacology, University of Virginia, Charlottesville, VA CHRISTOPHER N. HONDA • Department of Neuroscience, University of Minnesota, Minneapolis, MN W. G. HONER • Department of Psychiatry, University of British Colum- bia, Vancouver, Canada LUC JASMIN • Departments of Anatomy and the W. M. Keck Foundation Centre for Integrative Neuroscience and Neurological Surgery, University of California, San Francisco, CA KANWARJIT KELLEY • Departments of Anatomy and the W. M. Keck Foundation Centre for Integrative Neuroscience and Neurological Surgery, University of California, San Francisco, CA DOUGLAS A. LAPPI • President and Chief Scientific Officer, Advanced Targeting Systems, San Diego, CA K. J. LAYNE • Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, AZ ERIC MURILLO-RODRIGUEZ • Department of Neurology, Harvard Medical School and Veterans Administration Medical Center, West Roxbury, MA ix x Contributors A. J. NEWELL • Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, AZ PETER T. OHARA • Departments of Anatomy and the W. M. Keck Foundation Centre for Integrative Neuroscience and Neurological Surgery, University of California, San Francisco, CA M. E. POSTON • Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, AZ P. E. POTTER • Department of Pharmacology, Midwestern University, Glendale, AZ P. K. RAUSCHKOLB • Department of Pharmacology, Midwestern University, Glendale, AZ ROSALIND M. RIDLEY • Department of Experimental Psychology, School of Veterinary Medicine, Cambridge, UK SUE RITTER • Programs in Neuroscience, Washington State University, Pullman, WA A. E. ROHER • Longtine Center for Molecular Biology, Sun Health Research Institute, Sun City, AZ DAWNA M. SALTER • Programs in Neuroscience, University of Southern California, Los Angeles, CA MARTIN SARTER • Department of Psychology, University of Michigan, Ann Arbor, MI K. SAWADA • Department of Psychiatry, University of British Columbia, Vancouver, Canada REINHARD SCHLIEBS • Deparment of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Leipzig, Germany ANN M. SCHREIHOFER, PhD • Department of Physiology, Medical College of Georgia, Augusta, GA S. SCOTT • Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, AZ ` PRIYATTAM J. SHIROMANI, PhD • Department of Neurology, Harvard Medical School and Veterans Administration Medical Center, West Roxbury, MA FIORENZO STIRPE, MD • Dipartimento di Patologia Sperimentale, Universita di Bologna, Bologna, Italy RUTH L. STORNETTA, PhD • Department of Pharmacology, University of Virginia, Charlottesville, VA L. I. SUE • Sun Health Research Institute, Sun City, AZ LUCY VULCHANOVA • Deparment of Veterinary PathoBiology, University of Minnesota, St. Paul, MN JERENE J. WAITE • University of California, San Diego, CA, Veteran’s Medical Research Foundation, San Diego, CA Contributors xi D. G. WALKER • Laboratory for Neuroinflammation, Sun Health Research Institute, Sun City, AZ S. D. WEBSTER • Department of Molecular Biology and Biochemistry, University of California, Irvine, CA RONALD G. WILEY • Departments of Neurology and Pharmacology, Vanderbilt University School of Medicine and Neurology Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN
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