progress in parkinson research

PROGRESS IN PARKINSON RESEARCH

PROGRESS IN PARKINSON RESEARCH

Edited by

Franz Hefti and William J. Weiner National Parkinson Foundation Miami, Florida

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data National Parkinson Foundation Symposium on Parkinson Research (1st: 1988: Miami Beach, Fla.) Progress in Parkinson research / edited by Franz Hefti and William J. Weiner. p. cm. Proceedings of the First National Parkinson Foundation Symposium on Parkinson Research, held January 25-26, 1988 in Miami, Florida. Bibliography: p. Includes index.

ISBN-I3: 978-1-4612-8068-2 DOl: 1O.1007J978-1-46I3-07594

e-ISBN-I3: 978-1-4613-07594

I. Parkinsonism - Pathophysiology - Congresses.2. Methylphenyltetrahydropyridine -Physiological effect-Congress. I. Hefti, Franz. II. Weiner, William J. III. Title. 88-30731 RC382.N37 1988 616.8'33 -dcl9 CIP

Proceedings of the First National Parkinson Foundation Symposium on Parkinson Research, held January 25-26, 1988, in Miami, Florida © 1988 Plenum Press, New York

Softcover reprint ofthe hardcover 1st edition 1988 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 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

PREFACE

In the past five years significant progress has been made in our basic and clinical understanding of Parkinson's disease. The discovery that MPTP, a relatively simple molecule, is able to induce parkinsonism in otherwise healthy adult humans, and the recent interest in the possibility of "transplantation" procedures as a therapeutic modality in the treatment of Parkinson's disease have generated enormous interest in research related to Parkinson's disease. In this setting, the National Parkinson Foundation decided to organize a research meeting to bring together scientists actively engaged in research relevant to the study of Parkinson's disease, to accelerate its progress and to promote an exchange of ideas. This meeting took place in January 1988 at Key Biscayne, Florida. It was decided to publish the proceedings ofthis meeting to allow rapid documentation of the participants current findings and views regarding this rapidly evolving field. The structure of this volume follows the organization of the meeting and begins with a clinical and neuropathological review of current knowledge regarding Parkinson's disease. Since dopaminergic neurons playa major role in the pathophysiology of the disease, many of the contributions relate to some aspects of dopaminergic function including localization, regulation, and pharmacology of dopamine receptors. A special effort has been made to provide a summary of the present knowledge of the cellular biology of the dopaminergic neurons. There is extensive discussion of MPTP with particular emphasis on the role of potential other neurotoxins which might relate to Parkinson's disease. The topic of "transplantation" is addressed in several contributions. We thank the National Parkinson Foundation for making the meeting possible, its staff for excellent organization, and Merck, Sharp and Dohme for their generous grant which supported the meeting.

Franz Hefti and William J. Weiner Miami, July 1988

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CONTENTS

1. The Current Clinical Picture of Parkinson's Disease .................................... I Stewart A. Factor and William J. Weiner 2. The Neuropathology of Parkinson's Disease .......................................... II Lysia S. Forno 3. Anatomical and Pharmacological Comparisons between Dopamine D. and O2 Receptors in Mammalian CNS ........................................ 23 Eric K. Richfield, Anne B. Young, and John B. Penney 4. Architecture of Cholinergic Pre- and Postsynaptic Markers in the Primate Striatum ................................................. 31 Deborah C. Mash 5. Functional Anatomy of Dopamine Receptors ......................................... 39 G. Frederick Wooten and Joel M. Trugman 6. New Insights into the Regulation of Dopamine Receptor Subtypes and Their Roles in Behavior ............................................ 45 Ian Creese 7. Dopamine Receptors and Signal Transduction ......................................... 53 R. G. MacKenzie and J. W. Kebabian

8. The Therapeutic Potential of D. and O2 Dopamine Agonists in Parkinson's Disease ................................................. 61 Menek Goldstein and Ariel Y. Deutch 9. Isolation and Biochemical Characterization of the D. and O2 Dopamine Receptors .................................................. 67 Jay A. Gingrich, Susan E. Senogles, Nourdine Amilaiky, Wei K. Chang, Joel G. Berger, and Marc G. Caron 10. MPTP: Twenty Questions ............................................................ 77 J. William Langston 11. Search for Environment or Endogenous Neurotoxins Related to MPTP ................................................................ 85 S.P. Markey, H. Ikeda, S.-c. Yang, C.J. Markey, A.M. Marini, andJ.N. Johannessen 12. MPTP Neurotoxicity and the "Biochemical" Blood-Brain Barrier .......................................................................... 93 Sami I. Harik, Naji J. Riachi, and Joseph C. LaManna vii

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CONTENTS

13. Biochemistry ofthe Neurotoxic Action ofMPTP and What It May Teach Us about Etiology of Idiopathic Parkinsonism................... 101 Thomas P. Singer, Rona R. Ramsay, and Kathleen A. McKeown 14. A Biological Evaluation of Some 2' -Substituted Analogs ofMPTP ...................................................................... 113 Stephen K. Younster and Richard E. Heikkila 15. Hydrogen Peroxide Production in Dopamine Neurons: Implications for Understanding Parkinson's Disease Gerald Cohen and Mary Beth Spina

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16. Studies on the Toxicity of MPTP to Dopamine Neurons in Tissue and Cell Cultures ...................................................... 127 Catherine Mytilineou, Linda K. Friedman, and Peter Danias 17. Toxicity of Structural Analogs of I-Methyl-4-phenyl Pyridinium (MPP+) and Related Compounds on Dopaminergic Neurons in Culture ............................................................ 137 Franz Hefti, Juan R. Sanchez-Ramos, Patrick P. Michel, Simon Efange, and Berton C. Pressman 18. Mechanisms ofMPP+ Neurotoxicity: Oxyradical and Mitochondrial Inhibition Hypotheses ......................................... 145 Juan R. Sanchez-Ramos, Franz Hefti, Gary E. Hollinden, Thomas J. Sick, and Myron Rosenthal 19. Plasticity of Mesencephalic Dopaminergic Neurons ............................... 153 C.B. Jaeger 20. Trophic Effects of Striatal Proteins on Central Dopaminergic Neurons in Culture ........................................................... 163 Humberto B. Valdes, Doris Nonner, Dino Rulli, Leonard Gralnik, and John Barrett 21. Age-Related Changes of Dopaminergic Functions ................................. 173 Caleb E. Finch 22. Adrenal Medulla Transplants in Rodents and Nonhuman Primates: Regenerative Responses in the Host Brain .......................... 181 Don Marshall Gash, Massimo S. Fiandaca, Jeffrey H. Kordower, and John T. Hansen 23. Preliminary Evaluation and Report on Human Adrenal Medullary Grafting ........................................................... 187 Roy A.E. Bakay 24. Behavioral Performance Improves after Fetal Substantia Nigra Transplant in Bonnet Monkeys with MPTP Induced Parkinsonism ........................................................ 193 C.R. Freed, J .B. Richards, and M.L. Reite 25. Mechanisms of Action of Substantia Nigra and Adrenal Medulla Grafts ............................................................... 197 William J. Freed and Jill B. Becker 26. Recent Advances in Dopaminergic Implants ....................................... 205 U. Kopin, K.S. Bankiewicz, R.J. Plunkett, L. Porrino, D.M. Jacobowitz, W.T. London, and E.H. Oldfield

CONTENTS

27. Reversal of Experimental Parkinsonism in African Green Monkeys Following Fetal Dopamine Neuron Transplantation ............................................................... 211 T.J. Collier, D.E. Redmond Jr., R.H. Roth, J.D. Elsworth, andJ.R. SladekJr. 28. Transplantation of Human Dopaminergic Neurons in Parkinsonism: Experimental Reality and Future Clinical Feasibility ........................................................... 219 Ake Seiger, Lars Olson, Ingrid Stromberg, Marc Bygdeman, Menek Goldstein, and Barry Hoffer Index

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