Handbook of Neurotoxicity - Springer978-1-4614-5836-4/1.pdf · Neuroanatomie fonctionnelle: La cellule microgliale. He has also contributed to 12 other books and presented at over

Handbook of Neurotoxicity

Richard M. KostrzewaEditor

Handbook of Neurotoxicity

With 244 Figures and 38 Tables

EditorRichard M. KostrzewaDepartment of Biomedical SciencesQuillen College of MedicineEast Tennessee State UniversityJohnson City, TN, USA

ISBN 978-1-4614-5835-7 ISBN 978-1-4614-5836-4 (eBook)ISBN 978-1-4614-7458-6 (print and electronic bundle)DOI 10.1007/978-1-4614-5836-4Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2014931656

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Preface

Handbook of Neurotoxicity is a compendium intended to provide an overview on

neurotoxins. In addition, processes and mechanisms attending neuronal necrosis,

necroptosis, and apoptosis are discussed in detail. Also, glial perturbations, as these

relate to associated neuronal dysfunction, and both in vivo and in vitro methodo-

logical approaches toward the study and use of neurotoxins are discussed.

The first theme in the Handbook on selective neurotoxins provides a listing of

individual neurotoxins, with a description of relative selectivity of each, including

cellular mechanisms of action and overall neurologic and behavioral outcome

deriving from these neurotoxins’ effects. The second section, on dopamine-derived

neurotoxins, provides highlights of neuronal mechanisms associated with the

production of reactive dopamine quinones and semiquinones and reactive

oxygen/nitrogen species formed by the reactive dopamine analogs. These processes

and mechanisms are related to purported genesis of Parkinson’s disease.

The third section, on glutamate receptor agonists, is focused on the theme of

neuronal excitotoxicity as an outcome of over-excitation of neurons possessing

kainate receptors, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic

acid) receptors, and NMDA (N-methyl-D-aspartate) receptors. These excitotoxins

are discussed in detail as to their known and putative roles in neurodegenerative and

psychiatric disorders. Similarly, the roles of exogenous and endogenous glutamate

receptor antagonists as neuroprotectants and as neurotoxins per se are described.

The fourth section highlights the roles of neurotrophins in neuronal develop-

ment and relates their involvement in a host of neurotoxicity events in neurologic

and neurodegenerative disorders. The last section of the Handbook, focused on

diseases and disorders relevant to neurotoxins, describes processes and mechanisms

associated with specific neural disorders, including effects of some of the most

prominent neurotoxins in relation to human dysfunction. Additionally, impugned

neurotoxicity mechanisms in neurological disorders, protective strategies for

averting and delaying onset of neurologic and psychiatric disorders, and highlights

of newer strategies towards therapy are also discussed.

Handbook of Neurotoxicity is intended to be useful to students, scientists, and

clinicians as an initial introduction to neurotoxin-associated processes. Simulta-

neously, the Handbook is expected to be a valuable guide for those employing

specific neurotoxins as there are specific details on the use of individual neurotoxins

along with dosages, delineation of mechanisms of action, expected neuronal

v

degenerative effects, behavioral outcome, and possible duration of effect and

recovery from damage.

In essence, the Handbook is to represent an authoritative reference resource on

neurotoxins and neurotoxicity processes and mechanisms in the medical and

scientific arena.

vi Preface

Editor-in-Chief

Richard M. Kostrzewa, Ph.D., Dr.h.c., obtained a Ph.D. (1971) in Pharmacology

from the University of Pennsylvania. After positions as Research Pharmacologist at

the Veterans Administration Medical Center in New Orleans, Louisiana

(1971–1975); adjunct Assistant Professor in the Department of Pharmacology

at Tulane Medical School (1974–1976) and Department of Psychology at the

University of New Orleans (1974–1977); and Associate Professor at the Louisiana

University Medical Center in New Orleans (1975–1978), Dr. Kostrzewa joined the

faculty of Pharmacology at the newly established Quillen College of Medicine

at East Tennessee State University in Johnson City, Tennessee (Assoc. Prof./

Professor, 1978 to present). He actively collaborated in research for 20 years with

Prof. Ryszard Brus of the Medical University of Silesia in Katowice, Poland, where

Dr. Kostrzewa was Visiting Professor (1997–2003) and from which he received the

Doctorate Honoris Causa (2005). In 2001, Dr. Kostrzewa was made an Honorary

Member of the Polish Pharmacological Society. His research focus has remained on

selective neurotoxins, with applications in the areas of nerve regeneration, neuro-

degenerative disorders, and dopamine receptor supersensitivity. He has authored

and edited several books and more than 200 scientific papers, including the article co-

authored with Dr. David M. Jacobowitz, his former Dissertation Advisor, and desig-

nated as a “Citation Classic” in Current Contents: “Pharmacological Actions of

6-Hydroxydopamine.” Dr. Kostrzewa was the inaugural President of the Neurotox-

icity Society and served as the Society’s Treasurer for ten years. He has been Editor-

in-Chief of the journal Neurotoxicity Research from the time of its inception (1998).

vii

Section Editors

Trevor Archer obtained an Honour’s degree in Psychology and Physiology from

Newcastle-upon-Tyne University in 1974, and a Ph.D. from Uppsala University,

Uppsala, Sweden, in 1979. From 1978 to 1988, he was Head of CNS Drugs at Astra

L€akemedel AB. He was then appointed Professor and Chair of Biological Psychol-

ogy at the University of Gothenburg, Sweden. He has been Guest or Visiting

Professor at: the University of Hawaii at Manoa; Orebro University; Karlstad

University; Kalmar University; and Madrid University. He received an Outstanding

Lifetime Achievement Award from St. Joseph’s College, North Point in 2010, and

Honorary Doctorship, Professorship, and Membership Awards from the Polish

Academy of Science Pharmacological Society in 2013.

Gilles Guillemin is CORE Professor and Co-Director of the newly-created “MND

and Neurodegenerative Diseases Research Centre” at Macquarie University. He is

an Honorary Associate of the University of Sydney and the Visiting Senior

Research Fellow at the Australasian Research Institute, Sydney Adventist Hospital,

Wahroonga. Professor Guillemin has published over 110 papers and edited a book,

Neuroanatomie fonctionnelle: La cellule microgliale. He has also contributed to

12 other books and presented at over 90 conferences. Dr. Guillemin is heavily

involved in tryptophan research, as his group is one of the world’s leading research

groups working on neuroactive metabolites derived from tryptophan. He is the

newly-elected President of both the International Society for Tryptophan Research

(ISTRY) and the Neurotoxicity Society (NTS). His current research interest is

studying the involvement of tryptophan catabolism (via the kynurenine pathway)

in human neurodegenerative diseases such as amyotrophic lateral sclerosis, multi-

ple sclerosis, Parkinson’s disease, Alzheimer’s disease, and brain tumors.

Juan Segura-Aguilar studied chemistry with special mention in microbiology at

the University of Stockholm, Sweden, and received his bachelor’s degree in 1983.

In 1989, he received his Ph.D. in biochemistry from the University of Stockholm.

In 1999, he was awarded a stay at the University of Valencia by the European

Community. From 1993 to 1998, he was at Uppsala University, Sweden, where he

obtained “Docent” competence in 1994. In 1998, he moved to Chile and has been

Full Professor at the University of Chile. He has been awarded several competitive

research grants, including FONDECYT grants. Currently, he leads a research group

ix

that studies the role of dopamine oxidation in the degenerative process of the

nigrostriatal dopaminergic system. With Prof. Richard Kostrzewa, he founded and

organized the Neurotoxicity Society, and has also organized several international

NTS meetings, both regular and satellite.

Xin-Fu Zhou received his undergraduate medical degree from Third Military

Medical University in China in 1977, M.Sc. in neurology from Beijing PLA

Postgraduate College in 1982, and Ph.D. in biochemistry from the University of

Melbourne in 1990. He was awarded an Australian Postdoctoral Fellowship by the

Australian Research Council (ARC) in 1991 and completed his postdoctoral

research at Flinders University. Since 1997, he has been awarded four times

Research Fellowships and named Senior Research Fellow by the National Health

and Medical Research Council (NHMRC). He has been awarded numerous com-

petitive research grants by ARC and NHMRC. His main research interest has been

in neurotrophins and their receptors in neural development and in neurological

disorders. Recently, he is interested in functions of proneurotrophins and their

receptors in neurological diseases such as Alzheimer’s disease, spinal cord injury,

and depression. Currently, he is NHMRC Senior Research Fellow and Research

Chair in Neuroscience at University of South Australia.

x Section Editors

Contents

Volume 1

Part I Neurotoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Survey of Selective Neurotoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Richard M. Kostrzewa

Necroptosis, a Potential Therapeutic Target forNeurological Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Jing Chen, Richard M. Kostrzewa, and Xingshun Xu

RCSN Cell System for Identifying Dopaminergic Neurotoxicity . . . . . 95

Pablo Caviedes, Raul Caviedes, and Juan Segura-Aguilar

Microglia: Neuroprotective and Neurodestructive Properties . . . . . . . 109

G. Jean Harry and Christopher A. McPherson

6-Hydroxydopamine Lesioning of Dopamine Neurons in Neonataland Adult Rats Induces Age-Dependent Consequences . . . . . . . . . . . . 133

Sophia T. Papadeas and George R. Breese

Dopamine and L-dopa as Selective Endogenous Neurotoxins . . . . . . . . 199

Juan Segura-Aguilar, Ulises Ahumada-Castro, and Irmgard Paris

Nature of DSP-4-Induced Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . 219

Aleksandra Bortel

MPTP Neurotoxicity: Actions, Mechanisms, and AnimalModeling of Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237

Livia Pasquali, Elena Caldarazzo-Ienco, and Francesco Fornai

Cocaine as a Neurotoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277

Teresa Cunha-Oliveira, A. Cristina Rego, and Catarina R. Oliveira

5,6- and 5,7-Dihydroxytryptamines as SerotoninergicNeurotoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299

Justyna Paterak and Roman Stefanski

xi

20-NH2-MPTP: A Serotonin and Norepinephrine Neurotoxin . . . . . . . 327

Jason B. Ochroch, Amanda J. Bressler, Hongyan Yang, Dennis L. Murphy,

Stefanie C. Altieri, and Anne M. Andrews

Methamphetamine and MDMA Neurotoxicity: Biochemicaland Molecular Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347

Veronica Bisagno and Jean Lud Cadet

Glutamate as a Neurotoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365

Gabrielle N. Turski and Chrysanthy Ikonomidou

Domoic Acid as a Neurotoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399

Anabel Perez-Gomez and R. Andrew Tasker

Endogenous Kynurenic Acid and Neurotoxicity . . . . . . . . . . . . . . . . . . 421

Ewa M. Urbanska, Iwona Chmiel-Perzynska, Adam Perzynski,

Marek Derkacz, and Bjorn Owe-Larsson

Neurotoxicity in Psychostimulant and Opiate Addiction . . . . . . . . . . . 455

Ewa Niedzielska, Bartłomiej Rospond, Lucyna Pomierny-Chamioło,

Anna Sadakierska-Chudy, and Małgorzata Filip

Molecular Mechanism and Effects of Clostridial Neurotoxins . . . . . . . 513

Bal Ram Singh, Raj Kumar, and Shuowei Cai

Botulinum Neurotoxins as Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . 553

Raja Mehanna and Joseph Jankovic

Neurotoxic Effects, Mechanisms, and Outcome of192-IgG Saporin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591

Laura Petrosini, P. De Bartolo, and D. Cutuli

TRPV1 Activators (“Vanilloids”) as Neurotoxins . . . . . . . . . . . . . . . . . 611

Ashutosh Kumar, Rakesh Kumar Majhi, Manoj Yadav, Arpad Szallasi, and

Chandan Goswami

Volume 2

Part II Dopamine Chemistry and Parkinson Disease . . . . . . . . . . . 637

6-Hydroxydopamine as Preclinical Model of Parkinson’s Disease . . . . 639

Maria F. Galindo, Sara Saez-Atienzar, Maria E. Solesio, and

Joaquın Jordan

Advances in Stem Cell Research for Parkinson Disease . . . . . . . . . . . . 653

Irmgard Paris, Ulises Ahumada-Castro, and Juan Segura-Aguilar

Alpha Synuclein in Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . 691

Christine Lund Kragh, Marina Romero-Ramos, Glenda Halliday, and

Poul Henning Jensen

xii Contents

Autophagic Pathways and Parkinson Disease . . . . . . . . . . . . . . . . . . . . 727

Miquel Vila and Marta Martınez-Vicente

Dopaminergic Neurons in Parkinson’s Disease . . . . . . . . . . . . . . . . . . . 753

Rui Daniel Prediger, Mariza Bortolanza, Ana Carolina de Castro Issy,

Bruno Lopes dos Santos, Elaine Del Bel, and Rita Raisman-Vozari

Iron Neurotoxicity in Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . 789

Marco T. Nunez, Pamela Urrutia, Natalia Mena, and Pabla Aguirre

Links Between Paraquat and Parkinson’s Disease . . . . . . . . . . . . . . . . 819

Rosa A. Gonzalez-Polo, Jose M. Bravo-San Pedro, Ruben Gomez-Sanchez,

Elisa Pizarro-Estrella, Mireia Niso-Santano, and Jose M. Fuentes

Manganese Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 843

Daiana Silva Avila, Robson Luiz Puntel, Vanderlei Folmer, Joao Batista

Teixeira Rocha, Ana Paula Marreilha dos Santos, and Michael Aschner

Mechanisms of Dopamine Oxidation and Parkinson’s Disease . . . . . . . 865

Juan Segura-Aguilar and Irmgard Paris

Neuroinflammation and Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . 885

F. Ros-Bernal, J. E. Yuste, E. Tarragon, V. Ortiz, A. Gomez, C. M. Ros,

E. Fernandez-Villalba, and M. T. Herrero

Neuromelanin and Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . 913

Giorgia Greco

Neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) as a Parkinson’s Disease Model . . . . . . . . . . . . . . . . . . . . . . . . 933

H. Nakayama, T. Ito, Y. Shibui, T. Sai, K. Uchida, and X. J. He

N-Methyl-(R) Salsolinol and the Enzymes Catalyzing its Synthesisand Metabolism in Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . 953

Makoto Naoi and Wakako Maruyama

Regulation of DA Homeostasis and Role of VMAT2 in DA-InducedNeurodegeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 973

Eugene V. Mosharov

Rotenone as Preclinical Model Compound in Parkinson Disease . . . . . 995

Jason R. Cannon and J. Timothy Greenamyre

Part III Glutamate Receptor Agonists and Antagonists . . . . . . . . 1013

Concept of Excitotoxicity via Glutamate Receptors . . . . . . . . . . . . . . . 1015

Juan C. Pina-Crespo, Sara Sanz-Blasco, and Stuart A. Lipton

Role of Ionotropic Glutamate Receptors in Neurodegenerative andOther Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1039

Lotten Ragnarsson, Peter R. Dodd, and Matthew R. Hynd

Contents xiii

Ionotropic Receptors in the Central Nervous System andNeurodegenerative Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1071

Nady Braidy, Anne Poljak, Tharusha Jayasena, Gilles J. Guillemin, and

Perminder Sachdev

Glutamate Neurotoxicity, Transport and Alternate Splicing ofTransporters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1093

Aven Lee, Shannon Beasley, and David V. Pow

AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1115

M. Kaul

Cancer-Mediated Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155

Andrzej Stepulak, Radosław Rola, and Krzysztof Polberg

Drug Treatments for Alzheimer’s Disease: Hopesand Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173

Nady Braidy, Anne Poljak, Tharusha Jayasena, and Perminder Sachdev

Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191

Stjepana Kovac and Matthew C. Walker

Excitotoxicity and Amyotrophic Lateral Sclerosis . . . . . . . . . . . . . . . . 1209

Kim A. Staats and Ludo Van Den Bosch

Excitotoxicity and Axon Degeneration . . . . . . . . . . . . . . . . . . . . . . . . . 1223

Anna E. King and James C. Vickers

Excitotoxicity in HIV Associated Neurocognitive Disorders . . . . . . . . . 1247

Belinda Cruse and Bruce J. Brew

Excitotoxicity in the Pathogenesis of Autism . . . . . . . . . . . . . . . . . . . . . 1267

M. M. Essa, N. Braidy, S. Subash, R. K. Vijayan, and G. J. Guillemin

Glutamate and Neurodegeneration in the Retina . . . . . . . . . . . . . . . . . 1273

Thomas E. Salt

Glutamate in the Pathogenesis of Gliomas . . . . . . . . . . . . . . . . . . . . . . 1287

Nady Braidy, Anne Poljak, Tharusha Jayasena, Seray Adams, and

Perminder Sachdev

Glutamate Neurotoxicity Related to Energy Failure . . . . . . . . . . . . . . . 1299

Arne Schousboe

Glutamatergic Receptors in Parkinson’s Disease . . . . . . . . . . . . . . . . . 1311

A. Sampedro, E. Tarragon, J. E. Yuste, F. Ros-Bernal, V. Ortiz,

C. M. Campuzano, A. Gomez, C. M. Ros, E. Fernandez-Villalba, and

M. T. Herrero

Lead and Excitotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1341

Abdur Rahman

xiv Contents

MS and Excitotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1371

Chai K. Lim

Neuroprotectants Targeting NMDA Receptor Signaling . . . . . . . . . . . 1381

Sandra M. Vetiska and Michael Tymianski

Neuroprotection by Kynurenine Metabolites . . . . . . . . . . . . . . . . . . . . 1403

Zsofia Majlath, Levente Szalardy, Denes Zadori, Peter Klivenyi,

Ferenc F€ulop, Jozsef Toldi, and Laszlo Vecsei

Neuroprotective Strategies in Amyotrophic Lateral Sclerosis:Modulation of Neurotransmittory and Neurotrophic Input toMotor Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1417

Pierre-Francois Pradat and Luc Dupuis

Neurotoxicity and ALS: Insights into Pathogenesis . . . . . . . . . . . . . . . 1435

Steve Vucic and Matthew C. Kiernan

Neurotoxicity and Neuroprotection in Spinal Cord Injury . . . . . . . . . . 1457

Renee Morris

Neurotoxicity and Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1483

Victoria O’Collins, David Howells, and Romesh Markus

Neurotoxicity in Huntington Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 1511

C. T. Loy and A. J. Hannan

Neurotoxicity: A Complex Multistage Process InvolvingDifferent Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1525

Ewa Niedzielska, Bartłomiej Rospond, Lucyna Pomierny-Chamioło,

Anna Sadakierska-Chudy, and Małgorzata Filip

Quinolinate and Related Excitotoxins: Mechanisms of Neurotoxicityand Disease Relevance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1543

Jonas I. Addae and Trevor W. Stone

Role of Neurotoxicity in Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . 1567

Irena Smaga, Weronika Krzyzanowska, Bartosz Pomierny,

Bogusława Budziszewska, Andrzej Pilc, and Gabriel Nowak

Volume 3

Part IV Neurotrophins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1595

Amyloid-Beta, BDNF, and the Mechanism of Neurodegenerationin Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1597

Elyse Rosa and Margaret Fahnestock

Contents xv

BDNF V66M Polymorphism and Brain Functions . . . . . . . . . . . . . . . . 1621

Zhe-Yu Chen

Blood Brain-Derived Neurotrophic Factor Levels andMood Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1633

Reiji Yoshimura and Jun Nakumura

Neuroprotection in Demyelinating Diseases: The TherapeuticPotential of the Neurotrophins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1643

Junhua Xiao, Richard A. Hughes, and Simon S. Murray

Neurotrophic Factors and Ethanol Neurotoxicity . . . . . . . . . . . . . . . . . 1671

Margaret I. Davis

Neurotrophic Factors and NeuroAIDS: A Lesson from Brain-DerivedNeurotrophic Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1733

Alessia Bachis, Valeriya Avdoshina, Seung T. Lim, and Italo Mocchetti

Neurotrophic Therapy for ALS/MND . . . . . . . . . . . . . . . . . . . . . . . . . . 1755

Mary-Louise Rogers

Neurotrophins and p75NTR in Axonal Regenerationand Myelination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1787

Matt S. Ramer, Simon A. Bedard, and Angela L. M. Scott

Neurotrophins and Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1805

Ru-Ping Dai and Xin-Fu Zhou

Neurotrophin Signaling in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1825

Fei Tan, Carol J. Thiele, and Zhijie Li

NGF and Immune Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1849

Luisa Bracci-Laudiero and Luigi Manni

NGF/P75 in Cell Cycle and Tetraploidy . . . . . . . . . . . . . . . . . . . . . . . . 1877

Noelia Lopez-Sanchez, Marıa Carmen Ovejero-Benito,

Claudia Rodrıguez-Ruiz, and Jose Marıa Frade

p75NTR Processing and Signaling: Functional Role . . . . . . . . . . . . . . . 1899

Ramiro D. Almeida and Carlos B. Duarte

p75NTR: A Molecule with Multiple Functions in Amyloid-BetaMetabolism and Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1925

Yan-Jiang Wang, Fan Zeng, Khalil Saadipour, Jian-Jun Lu, and

Xin-Fu Zhou

Seizures Tip the Balance of Neurotrophin Signaling TowardNeuronal Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1945

Wilma J. Friedman, Audrey P. Le, Soyoung Choi, and Marta Volosin

xvi Contents

Synthesis, Trafficking and Release of BDNF . . . . . . . . . . . . . . . . . . . . . 1955

Jian-Jun Lu, Miao Yang, Ying Sun, and Xin-Fu Zhou

Trafficking of Neurotrophins and Their Receptors andPathological Significance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1973

Christopher S. von Bartheld

Part V Diseases and Disorders Relevant to Neurotoxins . . . . . . . 2001

Drug Abuse Neurotoxicity: Alcohol and Nicotine asDevelopmental Stressors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2003

Trevor Archer, Serafino Ricci, and Max Rapp-Ricciardi

Experimental Approach to Alzheimer Disease . . . . . . . . . . . . . . . . . . . 2025

M. Salkovic-Petrisic, S. Hoyer, and Peter Riederer

Fusion Models and “Fusioning” in Parkinsonism: Protection andRestoration by Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2047

Trevor Archer and Anders Fredriksson

Iron-Induced Dopaminergic Cell Death In Vivo as a Model ofParkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2065

Manfred Gerlach, Kay L. Double, and Peter Riederer

Molecular, Cellular, and Behavioural Effects Produced by PerinatalAsphyxia: Protection by Poly (ADP-Ribose) Polymerase 1 (PARP-1)Inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2075

T. Neira-Pena, P. Espina-Marchant, E. Rojas-Mancilla, D. Esmar,

C. Kraus, V. Munoz, R. Perez, B. Rivera, D. Bustamante,

J. L. Valdes, M. Hermoso, P. Gebicke-Haerter, P. Morales, and

M. Herrera-Marschitz

MPTP: Advances from an Evergreen Neurotoxin . . . . . . . . . . . . . . . . . 2099

Anna R. Carta, Augusta Pisanu, Carlos Barcia, and M. T. Herrero

Nanomedicines for Nervous System Diseases . . . . . . . . . . . . . . . . . . . . 2125

Dongwei Guo, JoEllyn M. McMillan, and Howard E. Gendelman

Neurodegenerative Aspects of Multiple System Atrophy . . . . . . . . . . . 2157

Rowan Radford, Mathew Wong, and Dean L. Pountney

Neurotoxic Vulnerability Underlying SchizophreniaSpectrum Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2181

Trevor Archer, Ulla Karilampi, Serafino Ricci, and M. Rapp-Ricciardi

Neurotoxicity of Methamphetamine . . . . . . . . . . . . . . . . . . . . . . . . . . . 2207

Rosario Moratalla, Sara Ares-Santos, and Noelia Granado

Contents xvii

Pathophysiology of Obsessive-Compulsive Disorder: Insights fromNormal Function and Neurotoxic Effects of Drugs,Infection, and Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2231

Henry Szechtman, Sohel Shivji, and Erik Z. Woody

Physical Exercise as Intervention in Parkinsonism . . . . . . . . . . . . . . . . 2255

Trevor Archer and Anders Fredriksson

Protective Agents in Parkinson’s Disease: Caffeine and AdenosineA2A Receptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2281

Nicola Simola, Annalisa Pinna, Lucia Frau, and Micaela Morelli

Stem Cell Therapies for Age Associated Neurodegeneration . . . . . . . . 2299

Stephanie Merchant, Sarah Stegeman, and Kiminobu Sugaya

Tardive Dyskinesia: Outcome of Antipsychotic Treatment andBrain Damage? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2315

Richard M. Kostrzewa, John P. Kostrzewa, and Ryszard Brus

Pathogenesis of Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 2327

Rudy J. Castellani and George Perry

Potential Therapeutic Effects of Statins in Alzheimer’s Disease . . . . . . 2339

Cesare Mancuso, Elizabeth Head, Eugenio Barone, Marzia Perluigi,

Paolo Preziosi, and D. Allan Butterfield

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2355

xviii Contents

Contributors

Seray Adams School of Medical Sciences, Faculty of Medicine, University of

New South Wales, Sydney, Australia

Jonas I. Addae Department of Preclinical Sciences, University of the West Indies,

St Augustine, Trinidad and Tobago

Pabla Aguirre Department of Biology, Faculty of Sciences, University of Chile,

Casilla, Santiago, Chile

Ulises Ahumada-Castro Program of Molecular and Clinical Pharmacology,

ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

Ramiro D. Almeida Center for Neuroscience and Cell Biology (CNC), University

of Coimbra, Coimbra, Portugal

Stefanie C. Altieri David Geffen School of Medicine, Department of Chemistry

and Biochemistry, Semel Institute for Neuroscience and Human Behavior, and

Hatos Center for Neuropharmacology, University of California, Los Angeles,

CA, USA

Anne M. Andrews David Geffen School of Medicine, Department of Chemistry



CA, USA

Trevor Archer Department of Psychology, University of Gothenburg,

Gothenburg, Sweden

Sara Ares-Santos Instituto Cajal, Consejo Superior de Investigaciones Cientıficas

(CSIC) and CIBERNED, ISCIII, Madrid, Spain

Michael Aschner Department of Pediatrics, Vanderbilt University, Nashville,

TN, USA

Department of Molecular Pharmacology, Albert Einstein College of Medicine,

Bronx, NY, USA

Valeriya Avdoshina Department of Neuroscience, Georgetown University

Medical Center, Washington, DC, USA

xix

Daiana Silva Avila Universidade Federal do Pampa, Uruguaiana, RS, Brazil

Alessia Bachis Department of Neuroscience, Georgetown University Medical

Center, Washington, DC, USA

Carlos Barcia Clinical and Experimental Neuroscience / Centro de Investigacion

Biomedica en Red de Enfermedades Neurodegenerativas (NiCE–CIBERNED),

School of Medicine, University of Murcia, Murcia, Spain

Eugenio Barone Institute of Pharmacology, Catholic University School of

Medicine, Rome, Italy

Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown

Center on Aging, University of Kentucky, Lexington, KY, USA

Shannon Beasley UQ Centre for Clinical Research, The University of

Queensland, Brisbane, QLD, Australia

Simon A. Bedard International Collaboration on Repair Discoveries, The

University of British Columbia, Vancouver, BC, Canada

Veronica Bisagno Instituto de Investigaciones Farmacologicas (ININFA-UBA-

CONICET), Buenos Aires, Argentina

Aleksandra Bortel Departments of Neurology, Neurosurgery, and Biomedical

Engineering, Montreal Neurological Institute, McGill University, Montreal, QC,

Canada

Mariza Bortolanza Departamento MFP-Fisiologia, Faculdade de Odontologia de

Ribeirao Preto, Universidade de Sao Paulo (USP), Center for Interdisciplinary

Research on Applied Neurosciences (NAPNA), Ribeirao Preto, SP, Brazil

Luisa Bracci-Laudiero Institute of Translational Pharmacology, National

Research Council of Italy (CNR), Rome, Italy

Nady Braidy Centre for Healthy Brain Ageing, School of Psychiatry, University

of New South Wales, Sydney, NSW, Australia

Jose M. Bravo-San Pedro Departamento de Bioquımica y Biologıa Molecular y

Genetica, Facultad de Enfermerıa y TO, Centro de Investigacion Biomedica en Red

sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad de

Extremadura, Caceres, Spain

George R. Breese Department of Psychiatry and Pharmacology, Bowles Center

for Alcohol Studies, UNC School of Medicine, Chapel Hill, NC, USA

Amanda J. Bressler David Geffen School of Medicine, Department of Chemistry



CA, USA

xx Contributors

Bruce J. Brew St. Vincent’s Centre for Applied Medical Research, Darlinghurst,

NSW, Australia

University of New South Wales, Sydney, Australia

Departments of Neurology and HIV Medicine, St. Vincent’s Hospital, Sydney,

NSW, Australia

Ryszard Brus Department of Nursing, High School of Strategic Planning,

Dabrowa Gornicza, Poland

Bogusława Budziszewska Department of Toxicology, Jagiellonian University

Medical College, Krakow, Poland

Institute of Pharmacology, Polish Academy of Sciences and Center of Excellence in

Neuropsychopharmacology, Krakow, Poland

D. Bustamante Millennium Institute BNI-Chile, Program of Molecular and Clinical

Pharmacology, ICBM, BNI, Medical Faculty, University of Chile, Santiago, Chile

D. Allan Butterfield Department of Chemistry, Center of Membrane Sciences,

and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA

Jean Lud Cadet NIDA Intramural Program, Molecular Neuropsychiatry Research

Branch, NIDA/NIH/DHHS, Baltimore, MD, USA

Shuowei Cai National Botulinum Research Center, and Department of Chemistry

and Biochemistry, University of Massachusetts Dartmouth, Dartmouth, MA, USA

Elena Caldarazzo-Ienco Clinical Neurology, University of Pisa, Pisa, Italy

C. M. Campuzano Clinical and Experimental Neuroscience (NiCE–CIBERNED),

School of Medicine, Campus de Espinardo, University of Murcia, Murcia, Spain

Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas

(CIBERNED), School of Medicine, University of Murcia, Murcia, Spain

Predepartmental Unit of Medicine, School of Health Sciences, Universitat Jaume I,

Castellon, Spain

Jason R. Cannon School of Health Sciences, Purdue University, West Lafayette,

IN, USA

Anna R. Carta Department of Biomedical Sciences, University of Cagliari,

Cagliari, Italy

Rudy J. Castellani Division of Neuropathology, University of Maryland,

Baltimore, MD, USA

Pablo Caviedes Program of Molecular and Clinical Pharmacology, ICBM,

Faculty of Medicine, University of Chile, Santiago, Chile

Contributors xxi

Raul Caviedes Program of Molecular and Clinical Pharmacology, ICBM, Faculty

of Medicine, University of Chile, Santiago, Chile

Jing Chen Department of Neurology, The Second Affiliated Hospital of Soochow

University, Suzhou City, Jiangsu, China

The Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, China

Zhe-Yu Chen Department of Neurobiology, School of Medicine, Shandong

University, Jinan, Shandong, China

Iwona Chmiel-Perzynska Laboratory of Cellular and Molecular Pharmacology,

Department of Experimental and Clinical Pharmacology, Medical University of

Lublin, Lublin, Poland

Soyoung Choi Department of Biological Sciences, Rutgers, The State University

of New Jersey, Newark, NJ, USA

Belinda Cruse Department of Neurology, St. Vincent’s Hospital, Sydney,

NSW, Australia

Teresa Cunha-Oliveira Center for Neuroscience and Cell Biology (CNC),

University of Coimbra, Coimbra, Portugal

D. Cutuli I.R.C.C.S. Santa Lucia Foundation, Rome, Italy

Ru-Ping Dai Department of Anesthesia, The Second Xiang-Ya Hospital of

Central South University, Changsha, Hunan Province, China

Margaret I. Davis Section on Synaptic Pharmacology, Laboratory for Integrative

Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National

Institutes of Health, Bethesda, MD, USA

P. De Bartolo Department of Psychology, Sapienza University of Rome,

Rome, Italy

I.R.C.C.S. Santa Lucia Foundation, Rome, Italy

Ana Carolina de Castro Issy Departamento MFP-Fisiologia, Faculdade de

Odontologia de Ribeirao Preto, Universidade de Sao Paulo (USP), Center for

Interdisciplinary Research on Applied Neurosciences (NAPNA), Ribeirao Preto,

SP, Brazil

Elaine Del Bel Departamento MFP-Fisiologia, Faculdade de Odontologia de

Ribeirao Preto, Universidade de Sao Paulo (USP), Center for Interdisciplinary

Research on Applied Neurosciences (NAPNA), Ribeirao Preto, SP, Brazil

Marek Derkacz Department of Endocrinology, Medical University of Lublin,

Lublin, Poland

Peter R. Dodd School of Chemistry andMolecular Biosciences, The University of

Queensland, St. Lucia Campus, Brisbane, Australia

xxii Contributors

Ana Paula Marreilha dos Santos Department of Toxicology and Food Sciences,

Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

Bruno Lopes dos Santos Department of Neurosciences and Behavior Sciences,

Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP,

Brazil

Kay L. Double The University of Sydney, Discipline of Biomedical Science,

School of Medical Science, Sydney Medical School, Sydney, Australia

Carlos B. Duarte Center for Neuroscience and Cell Biology (CNC) and

Department of Life Sciences, University of Coimbra, Coimbra, Portugal

Luc Dupuis INSERM, U1118, Faculte de Medecine, Mecanismes centraux et

peripheriques de la neurodegenerescence, Universite de Strasbourg, Strasbourg,

France

D. Esmar Millennium Institute BNI-Chile, Program of Molecular and Clinical

Pharmacology, ICBM, BNI, Medical Faculty, University of Chile, Santiago,

Chile

P. Espina-Marchant Millennium Institute BNI-Chile, Program of Molecular and

Clinical Pharmacology, ICBM, BNI, Medical Faculty, University of Chile,

Santiago, Chile

M. M. Essa Department of Food Science and Nutrition, College of Agriculture

and Marine Sciences, Sultan Qaboos University, Muscat, Oman

Margaret Fahnestock Department of Psychiatry and Behavioural Neurosciences,

McMaster University, Hamilton, ON, Canada

E. Fernandez-Villalba Clinical and Experimental Neuroscience (NiCE–

CIBERNED), School of Medicine, Campus de Espinardo, University of Murcia,

Murcia, Spain



Małgorzata Filip Department of Toxicology, Faculty of Pharmacy, Jagiellonian

University, Krakow, Poland

Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish

Academy of Sciences, Krakow, Poland

Vanderlei Folmer Universidade Federal do Pampa, Uruguaiana, RS, Brazil

Francesco Fornai Human Anatomy, University of Pisa, Pisa, Italy

Neuromed, I.R.C.C.S, Pozzilli, IS, Italy

Jose Marıa Frade Instituto Cajal, Consejo Superior de Investigaciones Cientıficas

(CSIC), Madrid, Spain

Contributors xxiii

Lucia Frau Department of Biomedical Sciences, University of Cagliari, Cagliari,

Italy

Anders Fredriksson Department of Neuroscience, Psychiatry, Ulleraker,

University Hospital, Uppsala, Sweden

Wilma J. Friedman Department of Biological Sciences, Rutgers, The State

University of New Jersey, Newark, NJ, USA

Jose M. Fuentes Departamento de Bioquımica y Biologıa Molecular y Genetica,

Facultad de Enfermerıa y TO, Centro de Investigacion Biomedica en Red sobre

Enfermedades Neurodegenerativas (CIBERNED), Universidad de Extremadura,

Caceres, Spain

Ferenc F€ulop Institute of Pharmaceutical Chemistry and Research Group of

Stereochemistry, Hungarian Academy of Sciences, University of Szeged, Szeged,

Hungary

Maria F. Galindo Unidad de Neuropsicofarmacologıa Traslacional, Complejo

Hospitalario Universitario de Albacete, Albacete, Spain

Pharmaceutical Technology School of Pharmacy, University of Castilla-La

Mancha, Albacete, Spain

P. Gebicke-Haerter Millennium Institute BNI-Chile, Program of Molecular and


Santiago, Chile

Department of Psychopharmacology, Central Institute of Mental Health,

Mannheim, Germany

Howard E. Gendelman Department of Pharmacology and Experimental

Neuroscience, University of Nebraska Medical Center, NE, USA

Manfred Gerlach University of W€urzburg, Department of Child and Adolescent

Psychiatry, Psychosomatics and Psychotherapy, Laboratory for Clinical

Neurobiology, W€urzburg, Germany

A. Gomez Clinical and Experimental Neuroscience (NiCE–CIBERNED),

School of Medicine, Campus de Espinardo, University of Murcia, Murcia,

Spain

Centro de Investigacion Biomedica en Red de Enfermedades

Neurodegenerativas (CIBERNED), School of Medicine, University of Murcia,

Murcia, Spain

Ruben Gomez-Sanchez Departamento de Bioquımica y Biologıa Molecular y

Genetica, Facultad de Enfermerıa y TO, Centro de Investigacion Biomedica en

Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad de


xxiv Contributors

Rosa A. Gonzalez-Polo Departamento de Bioquımica y Biologıa Molecular y




Chandan Goswami National Institute of Science Education and Research,

Institute of Physics Campus, Bhubaneswar, Orissa, India

Noelia Granado Instituto Cajal, Consejo Superior de Investigaciones Cientıficas

(CSIC) and CIBERNED, ISCIII, Madrid, Spain

Giorgia Greco Analytical Research Group, Wissenschaftszentrum

Weihenstephan, Technische Universit€at M€unchen, Freising, Germany

J. Timothy Greenamyre Pittsburgh Institute for Neurodegenerative Diseases,

University of Pittsburgh, Pittsburgh, PA, USA

Gilles J. Guillemin St. Vincent’s Centre for Applied Medical Research,

St. Vincent’s Hospital, Sydney, Australia

Neuropharmacology Group, MND and Neurodegenerative Diseases Research

Centre, Macquarie University, North Ryde, NSW, Australia

Dongwei Guo Departments of Pharmaceutical Sciences, University of Nebraska

Medical Center, Omaha, NE, USA

Glenda Halliday Neuroscience Research Australia and University of New South

Wales, Sydney, NSW, Australia

A. J. Hannan The Florey Institute of Neuroscience and Mental Health, The

University of Melbourne, Melbourne, Australia

G. Jean Harry Neurotoxicology Group, National Toxicology Program

Laboratory, National Institute of Environmental Health Sciences, Research

Triangle Park, NC, USA

X. J. He Department of Veterinary Pathology, Graduate School of Agricultural

and Life Sciences, The University of Tokyo, Tokyo, Japan

Elizabeth Head Department of Molecular and Biomedical Pharmacology,

and Sanders-Brown Center on Aging, University of Kentucky, Lexington,

KY, USA

M. Hermoso Millennium Institute BNI-Chile, Program of Molecular and Clinical


M. Herrera-Marschitz Millennium Institute BNI-Chile, Program of Molecular

and Clinical Pharmacology, ICBM, BNI, Medical Faculty, University of Chile,

Santiago, Chile

Contributors xxv

M. T. Herrero Clinical and Experimental Neuroscience (NiCE–CIBERNED),





Castellon, Spain

David Howells Florey Neuroscience Institutes, Melbourne Brain Centre,

Heidelberg, VIC, Australia

S. Hoyer Department of Pathology, University of Heidelberg, Heidelberg,

Germany

Richard A. Hughes Department of Pharmacology, University of Melbourne,

VIC, Australia

Matthew R. Hynd School of Chemistry and Molecular Biosciences, The

University of Queensland, St. Lucia Campus, Brisbane, Australia

Chrysanthy Ikonomidou Department of Neurology, University of Wisconsin,

Madison, WI, USA

T. Ito Department of Veterinary Pathology, Graduate School of Agricultural and

Life Sciences, The University of Tokyo, Tokyo, Japan

Joseph Jankovic Parkinson’s Disease Center and Movement Disorders Clinic,

Department of Neurology, Baylor College of Medicine, Houston, TX, USA

Tharusha Jayasena Centre for Healthy Brain Ageing, School of Psychiatry,

University of New South Wales, Sydney, NSW, Australia

Poul Henning Jensen Department of Biomedicine, Aarhus University, Aarhus C,

Denmark

Joaquın Jordan Grupo de Neurofarmacologıa, Facultad de Medicina de Albacete,

Universidad de Castilla-La Mancha, Albacete, Spain

Ulla Karilampi Department of Psychiatry/Psychosis, Sahlgrenska University

Hospital, Gothenburg, Sweden

M. Kaul Infectious and Inflammatory Disease Center, Sanford-Burnham Medical

Research Institute, La Jolla, CA, USA

Matthew C. Kiernan Bushell Professor of Neurology, Brain and Mind Research

Institute, University of Sydney, Sydney, Australia

Neuroscience Research Australia, Randwick, Sydney, NSW, Australia

Anna E. King Wicking Dementia Research and Education Centre, University of

Tasmania, Hobart, Tasmania, Australia

xxvi Contributors

Peter Klivenyi Department of Neurology, University of Szeged, Szeged, Hungary

John P. Kostrzewa Department of Biomedical Sciences, Quillen College of

Medicine, East Tennessee State University, Johnson City, TN, USA

North Alabama ENT Associates, Huntsville, AL, USA

Richard M. Kostrzewa Department of Biomedical Sciences, Quillen College of

Medicine, East Tennessee State University, Johnson City, TN, USA

Stjepana Kovac UCL Institute of Neurology, University College London,

London, UK

Christine Lund Kragh Department of Biomedicine, Aarhus University, Aarhus C,

Denmark

C. Kraus Millennium Institute BNI-Chile, Program of Molecular and Clinical


Weronika Krzyzanowska Department of Toxicology, Jagiellonian University


Ashutosh Kumar National Institute of Science Education and Research, Institute

of Physics Campus, Bhubaneswar, Orissa, India

Raj Kumar National Botulinum Research Center and Department of Chemistry

and Biochemistry, University of Massachusetts Dartmouth, Dartmouth, MA, USA

Audrey P. Le Department of Biological Sciences, Rutgers, The State University


Aven Lee UQ Centre for Clinical Research, The University of Queensland,

Brisbane, QLD, Australia

Zhijie Li Cellular and Molecular Biology, Pediatric Oncology Branch, National

Cancer Institute, National Institute of Health, Bethesda, MD, USA

Chai K. Lim Department of Pharmacology, School of Medical Sciences,

University of New South Wales, Sydney, Australia

MND and Neurodegenerative Diseases Research Group, Macquarie University,

Sydney, Australia

Seung T. Lim Department of Neuroscience, Georgetown University Medical


Stuart A. Lipton Del E. Webb Center for Neuroscience, Aging, and Stem Cell

Research, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

Noelia Lopez-Sanchez Instituto Cajal, Consejo Superior de Investigaciones

Cientıficas (CSIC), Madrid, Spain

Contributors xxvii

C. T. Loy School of Public Health, The University of Sydney, Sydney, Australia

Huntington Disease Service, Westmead Hospital, Sydney, Australia

Jian-Jun Lu Division of Health Sciences, University of South Australia,

Adelaide, SA, Australia

Rakesh Kumar Majhi National Institute of Science Education and Research,

Institute of Physics Campus, Bhubaneswar, Orissa, India

ZsofiaMajlath Department of Neurology, University of Szeged, Szeged, Hungary

Cesare Mancuso Institute of Pharmacology, Catholic University School of


Luigi Manni Institute of Translational Pharmacology, National Research Council

of Italy (CNR), Rome, Italy

Romesh Markus Department of Neurology, St. Vincent’s Hospital, Darlinghurst,

Sydney, NSW, Australia

Marta Martınez-Vicente Neurodegenerative Diseases Research Group, Vall

d’Hebron Research Institute–CIBERNED, Barcelona, Spain

Department of Biochemistry and Molecular Biology, Autonomous University of

Barcelona (UAB), Barcelona, Spain

Wakako Maruyama Department of Cognitive Brain Science, National Research

Center for Geriatrics and Gerontology, Obu Aichi, Japan

JoEllyn M. McMillan Department of Pharmacology and Experimental

Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Christopher A. McPherson Neurotoxicology Group, National Toxicology

Program Laboratory, National Institute of Environmental Health Sciences,

Research Triangle Park, NC, USA

Raja Mehanna Parkinson’s Disease Center and Movement Disorders Clinic,

Department of Neurology, Baylor College of Medicine, Houston, TX, USA

Natalia Mena Department of Biology, Faculty of Sciences, University of Chile,


Stephanie Merchant College of Medicine, University of Central Florida,

Orlando, FL, USA

Italo Mocchetti Department of Neuroscience, Georgetown University Medical


P. Morales Millennium Institute BNI-Chile, Program of Molecular and


Santiago, Chile

xxviii Contributors

Rosario Moratalla Instituto Cajal, Consejo Superior de Investigaciones

Cientıficas (CSIC) and CIBERNED, ISCIII, Madrid, Spain

Micaela Morelli Department of Biomedical Sciences, University of Cagliari,

Cagliari, Italy

CNR Institute of Neuroscience, Cagliari, Italy

Renee Morris Translational Neuroscience Facility, School of Medical Sciences,

The University of New South Wales, Sydney, NSW, Australia

Eugene V. Mosharov Department of Neurology, Columbia University,

New York, NY, USA

V. Munoz Millennium Institute BNI-Chile, Program of Molecular and


Santiago, Chile

Dennis L. Murphy Laboratory of Clinical Science, National Institute of Mental

Health, National Institutes of Health, Bethesda, MD, USA

Simon S. Murray Department of Anatomy and Neuroscience, The University of

Melbourne, Parkville, VIC, Australia

H. Nakayama Department of Veterinary Pathology, Graduate School of

Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

Jun Nakumura Department of Psychiatry, School of Medicine, University of

Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan

Makoto Naoi Department of Neurosciences, Gifu International Institute of

Biotechnology, Kakamigahara Gifu, Japan

T. Neira-Pena Millennium Institute BNI-Chile, Program ofMolecular and Clinical


Ewa Niedzielska Department of Toxicology, Faculty of Pharmacy, Jagiellonian

University, Krakow, Poland

Mireia Niso-Santano Departamento de Bioquımica y Biologıa Molecular y




Gabriel Nowak Department of Pharmacobiology, Jagiellonian University


Institute of Pharmacology, Polish Academy of Sciences and Center of Excellence in

Neuropsychopharmacology, Krakow, Poland

Marco T. Nunez Department of Biology, Faculty of Sciences, University of Chile,


Contributors xxix

Victoria O’Collins Florey Neuroscience Institutes, Melbourne Brain Centre,

Heidelberg, VIC, Australia

Jason B. Ochroch David Geffen School of Medicine, Department of Chemistry



CA, USA

V. Ortiz Clinical and Experimental Neuroscience (NiCE–CIBERNED), School of

Medicine, Campus de Espinardo, University of Murcia, Murcia, Spain



Catarina R. Oliveira Center for Neuroscience and Cell Biology (CNC) and

Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Marıa Carmen Ovejero-Benito Instituto Cajal, Consejo Superior de

Investigaciones Cientıficas (CSIC), Madrid, Spain

Bjorn Owe-Larsson Department of Clinical Neuroscience, Karolinska Institutet,

Section of Psychiatry at Karolinska University Hospital Huddinge, Stockholm,

Sweden

Sophia T. Papadeas Chapel Hill, NC, USA

Irmgard Paris Program of Molecular and Clinical Pharmacology, ICBM,


Department of Basic Sciences, Santo Tomas University, Vina del Mar, Chile

Livia Pasquali Clinical Neurology, University of Pisa, Pisa, Italy

Justyna Paterak Department of Pharmacology and Physiology of the Nervous

System, Institute of Psychiatry and Neurology, Warsaw, Poland

R. Perez Millennium Institute BNI-Chile, Program of Molecular and Clinical

Pharmacology, ICBM, BNI, Medical Faculty, University of Chile, Santiago,

Chile

Anabel Perez-Gomez Department of Biomedical Sciences, University of Prince

Edward Island, Charlottetown, PEI, Canada

Marzia Perluigi Department of Biochemical Sciences, Faculty of Pharmacy and

Medicine, Sapienza University of Rome, Rome, Italy

George Perry Department of Biology and UTSA Neurosciences Institute,

The University of Texas at San Antonio, San Antonio, TX, USA

Adam Perzynski Department of Psychiatry, Medical University of Lublin,

Lublin, Poland

xxx Contributors

Laura Petrosini Department of Psychology, Sapienza University of Rome,

Rome, Italy

I.R.C.C.S. Santa Lucia Foundation, Rome, Italy

Andrzej Pilc Institute of Pharmacology, Polish Academy of Sciences and Center

of Excellence in Neuropsychopharmacology, Krakow, Poland

Jagiellonian University Medical College, Krakow, Poland

Juan C. Pina-Crespo Del E. Webb Center for Neuroscience, Aging, and

Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla,

CA, USA

Annalisa Pinna Department of Biomedical Sciences, University of Cagliari,

Cagliari, Italy

CNR Institute of Neuroscience, Cagliari, Italy

Augusta Pisanu CNR Institute of Neuroscience, Cagliari, Italy

Elisa Pizarro-Estrella Departamento de Bioquımica y Biologıa Molecular y




Krzysztof Polberg Department of Otolaryngology, MSW Hospital, Lublin,

Poland

Anne Poljak School of Medical Sciences, Faculty of Medicine and

Bioanalytical Mass Spectrometry Facility, University of New South Wales,

Sydney, Australia

Bartosz Pomierny Department of Toxicology, Jagiellonian University Medical

College, Krakow, Poland

Lucyna Pomierny-Chamioło Department of Toxicology, Faculty of Pharmacy,

Jagiellonian University, Krakow, Poland

Dean L. Pountney School of Medical Science and Griffith Health Institute,

Griffith University, Gold Coast, QLD, Australia

David V. Pow School of Medical Sciences and Health Innovations Research

Institute, RMIT University, Melbourne, VIC, Australia

Pierre-Francois Pradat Departement des Maladies du Systeme Nerveux,

AP-HP, Groupe Hospitalier Pitie-Salpetriere, UMR-678, INSERM-UPMC,

Paris, France

Rui Daniel Prediger Laboratorio Experimental de Doencas Neurodegenerativas,

Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC),

Florianopolis, SC, Brazil

Contributors xxxi

Paolo Preziosi Institute of Pharmacology, Catholic University School of


Robson Luiz Puntel Universidade Federal do Pampa, Uruguaiana, RS, Brazil

Rowan Radford Griffith Health Institute, Griffith University, Gold Coast, QLD,

Australia

Lotten Ragnarsson Institute for Molecular Bioscience, The University of

Queensland, Brisbane, QLD, Australia

Abdur Rahman Department of Food Science and Nutrition, College for Women,

Kuwait University, Safat, Kuwait

Rita Raisman-Vozari INSERM UMR 975 (ex U679), CNRS UMR 7225,

Universite Pierre et Marie Curie (UPMC), Centre de Recherche de l’Institut du

Cerveau et de la Moelle epiniere (CRICM), Therapeutique Experimentale de la

neurodegenerescence, Hopital de la Salpetriere, Paris, France

Matt S. Ramer International Collaboration on Repair Discoveries, The University

of British Columbia, Vancouver, BC, Canada

Max Rapp-Ricciardi Department of Psychology, University of Gothenburg,

Gothenburg, Sweden

A. Cristina Rego Center for Neuroscience and Cell Biology (CNC) and Faculty of

Medicine, University of Coimbra, Coimbra, Portugal

Serafino Ricci Department of Anatomy, Histology, Forensic Medicine and

Orthopaedics, Sapienza University of Rome, Rome, Italy

Peter Riederer University of W€urzburg, Department of Psychiatry,

Psychosomatics and Psychotherapy, and National Parkinson Foundation Centers

of Excellence for Neurodegenerative Diseases Research, Laboratory for Clinical

Neurochemistry, W€urzburg, Germany

B. Rivera Millennium Institute BNI-Chile, Program of Molecular and


Santiago, Chile

Joao Batista Teixeira Rocha Universidade Federal de Santa Maria, RS, Brazil

Claudia Rodrıguez-Ruiz Instituto Cajal, Consejo Superior de Investigaciones

Cientıficas (CSIC), Madrid, Spain

Mary-Louise Rogers Department of Human Physiology, Centre for Neuroscience,

School of Medicine, Flinders University, Adelaide, SA, Australia

E. Rojas-Mancilla Millennium Institute BNI-Chile, Program of Molecular and


Santiago, Chile

xxxii Contributors

Radosław Rola Department of Neurological Surgery, Medical University of


Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland

Marina Romero-Ramos Department of Biomedicine, Aarhus University,

Aarhus C, Denmark

C. M. Ros Clinical and Experimental Neuroscience (NiCE–CIBERNED), School

of Medicine, Campus de Espinardo, University of Murcia, Murcia, Spain




Castellon, Spain

F. Ros-Bernal Clinical and Experimental Neuroscience (NiCE–CIBERNED),





Castellon, Spain

Elyse Rosa Department of Psychiatry and Behavioural Neurosciences, McMaster

University, Hamilton, ON, Canada

Bartłomiej Rospond Department of Toxicology, Faculty of Pharmacy,

Jagiellonian University, Krakow, Poland

Khalil Saadipour Division of Health Sciences, University of South Australia,

Adelaide, SA, Australia

Perminder Sachdev Centre for Healthy Brain Ageing, School of Psychiatry,

University of New South Wales, Sydney, NSW, Australia

Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia

Anna Sadakierska-Chudy Laboratory of Drug Addiction Pharmacology,

Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland

Sara Saez-Atienzar Faculty of Medicine and Dentistry, Catholic University of

Valencia San Vicente Martir, Valencia, Spain

T. Sai Department of Veterinary Pathology, Graduate School of Agricultural and

Life Sciences, The University of Tokyo, Tokyo, Japan

M. Salkovic-Petrisic Department of Pharmacology and Croatian Institute for

Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia

Contributors xxxiii

Thomas E. Salt Department of Visual Neuroscience, UCL Institute of

Ophthalmology, London, UK

A. Sampedro Clinical and Experimental Neuroscience (NiCE–CIBERNED),




Sara Sanz-Blasco Del E. Webb Center for Neuroscience, Aging, and Stem Cell

Research, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

Arne Schousboe Department of Drug Design and Pharmacology, Faculty of

Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Angela L. M. Scott International Collaboration on Repair Discoveries, The

University of British Columbia, Vancouver, BC, Canada

Juan Segura-Aguilar Program of Molecular and Clinical Pharmacology, ICBM,


Y. Shibui Department of Veterinary Pathology, Graduate School of Agricultural


Sohel Shivji Department of Psychiatry and Behavioural Neurosciences, McMaster

University, Hamilton, ON, Canada

Nicola Simola Department of Biomedical Sciences, University of Cagliari,

Cagliari, Italy

Bal Ram Singh National Botulinum Research Center and Department of

Chemistry and Biochemistry, University of Massachusetts Dartmouth,

Dartmouth, MA, USA

Irena Smaga Department of Toxicology, Jagiellonian University Medical

College, Krakow, Poland

Maria E. Solesio Unidad de Neuropsicofarmacologıa Traslacional, Complejo

Hospitalario Universitario de Albacete, Albacete, Spain

Kim A. Staats Laboratory of Neurobiology and Leuven Research Institute of

Neurodegenerative Diseases (LIND), KU Leuven, Leuven, Belgium

Vesalius Research Center, VIB, Leuven, Belgium

Roman Stefanski Department of Pharmacology and Physiology of the Nervous

System, Institute of Psychiatry and Neurology, Warsaw, Poland

Sarah Stegeman College of Medicine, University of Central Florida, Orlando,

FL, USA

xxxiv Contributors

Andrzej Stepulak Department of Biochemistry and Molecular Biology, Medical

University of Lublin, Lublin, Poland

Department of Otolaryngology, MSW Hospital, Lublin, Poland

Trevor W. Stone Institute of Neuroscience and Psychology, University of

Glasgow, Glasgow, UK

S. Subash Department of Food Science and Nutrition, College of Agriculture and

Marine Sciences, Sultan Qaboos University, Muscat, Oman

Kiminobu Sugaya College of Medicine, University of Central Florida, Orlando,

FL, USA

Ying Sun School of Pharmacy and Medical Sciences, Faculty of Health Sciences,

University of South Australia, Adelaide, SA, Australia

Levente Szalardy Department of Neurology, University of Szeged, Szeged,

Hungary

Arpad Szallasi Monmouth Medical Center, Long Branch, NJ, USA

Henry Szechtman Department of Psychiatry and Behavioural Neurosciences,

McMaster University, Hamilton, ON, Canada

Fei Tan Department of Neurology, Shengjing Hospital of China Medical

University, Shenyang, China

E. Tarragon Clinical and Experimental Neuroscience (NiCE–CIBERNED),





Castellon, Spain

R. Andrew Tasker Department of Biomedical Sciences, University of Prince

Edward Island, Charlottetown, PEI, Canada

Carol J. Thiele Cellular and Molecular Biology, Pediatric Oncology Branch,

National Cancer Institute, National Institute of Health, Bethesda, MD, USA

Jozsef Toldi Department of Physiology, Anatomy and Neuroscience, University

of Szeged, Szeged, Hungary

Neuroscience Research Group of the Hungarian Academy of Sciences and

University of Szeged, Szeged, Hungary

Gabrielle N. Turski 2nd Faculty of Medicine, Charles University, Prague, Czech

Republic

Contributors xxxv

Michael Tymianski Neuroprotection Laboratory, Toronto Western Research

Institute, University Health Network, Toronto, ON, Canada

K. Uchida Department of Veterinary Pathology, Graduate School of Agricultural


Ewa M. Urbanska Laboratory of Cellular and Molecular Pharmacology,

Department of Experimental and Clinical Pharmacology, Medical University of


Department of Toxicology, Institute of Agricultural Medicine, Lublin, Poland

Pamela Urrutia Department of Biology, Faculty of Sciences, University of Chile,


J. L. Valdes Millennium Institute BNI-Chile, Program of Molecular and


Santiago, Chile

Ludo Van Den Bosch Laboratory of Neurobiology and Leuven Research Institute

of Neurodegenerative Diseases (LIND), KU Leuven, Leuven, Belgium

Vesalius Research Center, VIB, Leuven, Belgium

Laszlo Vecsei Department of Neurology, University of Szeged, Szeged, Hungary

Neuroscience Research Group of the Hungarian Academy of Sciences and

University of Szeged, Szeged, Hungary

Sandra M. Vetiska Neuroprotection Laboratory, Toronto Western Research

Institute, University Health Network, Toronto, ON, Canada

James C. Vickers Wicking Dementia Research and Education Centre, University

of Tasmania, Hobart, Tasmania, Australia

R. K. Vijayan Department of Food Science and Nutrition, College of Agriculture

and Marine Sciences, Sultan Qaboos University, Muscat, Oman

Miquel Vila Neurodegenerative Diseases Research Group, Vall d’Hebron

Research Institute–CIBERNED, Barcelona, Spain

Department of Biochemistry and Molecular Biology, Autonomous University of

Barcelona (UAB), Barcelona, Spain

Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

Marta Volosin Department of Biological Sciences, Rutgers, The State University


xxxvi Contributors

Christopher S. von Bartheld Department of Physiology and Cell Biology,

University of Nevada School of Medicine, Reno, NV, USA

Steve Vucic Sydney Medical School Westmead, University of Sydney, Sydney,

Australia

Neuroscience Research Australia, Randwick, Sydney, NSW, Australia

Matthew C. Walker UCL Institute of Neurology, University College London,

London, UK

Yan-Jiang Wang Department of Neurology, Daping Hospital, Third Military

Medical University, Daping, Chongqing, China

Mathew Wong Griffith Health Institute, Griffith University, Gold Coast, QLD,

Australia

Erik Z. Woody Department of Psychology, University of Waterloo, Waterloo,

ON, Canada

Junhua Xiao Department of Anatomy and Neuroscience, The University of

Melbourne, Parkville, VIC, Australia

Xingshun Xu Department of Neurology, The Second Affiliated Hospital of

Soochow University, Suzhou City, Jiangsu, China

The Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, China

Manoj Yadav National Institute of Science Education and Research, Institute of

Physics Campus, Bhubaneswar, Orissa, India

Hongyan Yang David Geffen School of Medicine, Department of Chemistry and

Biochemistry, Semel Institute for Neuroscience and Human Behavior, and Hatos

Center for Neuropharmacology, University of California, Los Angeles, CA, USA

Miao Yang School of Pharmacy and Medical Sciences, Faculty of Health

Sciences, University of South Australia, Adelaide, SA, Australia

Reiji Yoshimura Department of Psychiatry, School of Medicine, University of

Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan

J. E. Yuste Clinical and Experimental Neuroscience (NiCE–CIBERNED), School

of Medicine, Campus de Espinardo, University of Murcia, Murcia, Spain




Castellon, Spain

Contributors xxxvii

Denes Zadori Department of Neurology, University of Szeged, Szeged, Hungary

Fan Zeng Department of Neurology, Daping Hospital, Third Military Medical

University, Daping, Chongqing, China

Xin-Fu Zhou School of Pharmacy and Medical Sciences, Faculty of Health

Sciences, University of South Australia, Adelaide, SA, Australia

xxxviii Contributors

Documents

Handbook of Neurotoxicity - Springer978-1-4614-5836-4/1.pdf · Neuroanatomie fonctionnelle: La cellule microgliale. He has also contributed to 12 other books and presented at over