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Adenosine Susan Masino Detlev Boison ● Editors Adenosine A Key Link between Metabolism and Brain Activity Editors Susan Masino Detlev Boison Trinity College Legacy Research Institute Hartford, CT, USA Portland, OR, USA ISBN 978-1-4614-3902-8 ISBN 978-1-4614-3903-5 (eBook) DOI 10.1007/978-1-4614-3903-5 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2012943605 © Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. 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While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface For many years the “retaliatory metabolite” and neuromodulator adenosine has been recognized as an endogenous anticonvulsant and neuroprotective molecule. As the core molecule of ATP and of nucleic acids, adenosine forms a unique link among cell energy, gene regulation, and neuronal excitability. Adenosine has long been a highly coveted therapeutic target, and its actions at the A receptor subtype hold 1 well-established and profound therapeutic potential for conditions such as stroke, brain injury, pain, and epilepsy, among others. To date, receptor-based strategies to augment the therapeutic in fl uence of adenosine have been unable to harness its clinical potential, primarily due to side effects at identical peripheral adenosine receptors. Emerging evidence ignites new hope for adenosine-based therapies in the central nervous system. Parallel and converging lines of research include studies on the ongoing regulation of adenosine by nonpathological, physiologically relevant v vi Preface stimuli, by metabolism and astrocytes and also by exciting new cell-based approaches. All of these modes of regulation have detailed associated mechanisms established by basic research and, accordingly, proven or predicted clinical implications. In this book we assemble diverse recent research on regulating the in fl uence of adenosine in the central nervous system. We outline clinical implications and high- light emerging adenosine-based therapies. For example, the relationship between adenosine and the highly altered metabolic state during hibernation has important predictions for neuroprotection. As part of a major paradigm shift, we now under- stand that the regulation of extracellular adenosine by astrocytes is critical for normal sleep and could be pivotal for the prevention and treatment of epilepsy. In addition, there is an established functional relationship where adenosine and dopamine receptors form receptor heteromers and extend the clinical reach of the regulation of adenosine directly into the realm of dopaminergic disorders and neu- ropsychiatry. Finally, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy used to treat pediatric and medically refractory epilepsy for nearly 100 years. Although its ef fi cacy is well established, the key neural mechanisms underlying its success remained unclear, hindering development of analogous pharmacological solutions. Converging evidence points to a critical link between ketogenic metabolism and increased adenosine. Given its ubiquitous presence in the extracellular fl uid, and the central role of adenosine as both a metabolic sensor and an effector, it is not surprising that adenosine function and dysfunction in the central nervous system appears to be a common link between diverse neurological and neuropsychiatric conditions. The broad therapeutic implications of understanding the regulation of adenosine extend to acute and chronic neurological disorders as diverse as brain injury, epilepsy, pain, neuro- degenerative disorders, and dopamine-related disorders. Here we combine cellular and clinical evidence in an attempt to strengthen the conceptual underpinnings of this important research area and foster a broad and interdisciplinary perspective regarding the therapeutic potential and mechanisms associated with adenosine in the central nervous system. We would like to express our sincere thanks to all the authors for their excellent contributions and commitment for making this book possible. We thank them for their patience and adherence to editorial timelines. We thank the many experts who contributed to the peer-review process and the success of this publishing endeavor. We are indebted to Sue Crawford who provided invaluable assistance. Finally we wish to thank Simina Calin and Ann Avouris at Springer for their continued support and guidance. Hartford, CT, USA Susan Masino Portland, OR, USA Detlev Boison Contents Part I Introduction 1 Adenosine and Metabolism—A Brief Historical Note ......................... 3 Bertil B. Fredholm Part II Molecular Biology, Pharmacology, and Cell Biology of Adenosine 2 Adenosine Metabolism, Adenosine Kinase, and Evolution ................. 23 Jaoek Park and Radhey S. Gupta 3 Adenosine and Energy Metabolism—Relationship to Brain Bioenergetics ............................................................................. 55 Xuesong Chen, Liang Hui, and Jonathan D. Geiger 4 Adenosine and Autocrine Metabolic Regulation of Neuronal Activity ................................................................................ 71 Masahito Kawamura Jr. and David N. Ruskin 5 Physiologic and Metabolic Regulation of Adenosine: Mechanisms ............................................................................................. 87 Chris G. Dulla and Susan A. Masino 6 The Double-Edged Sword: Gaining Adenosine at the Expense of ATP. How to Balance the Books............................... 109 Stephanie zur Nedden, Alexander S. Doney, and Bruno G. Frenguelli 7 Downstream Pathways of Adenosine..................................................... 131 Ana M. Sebastião, Sofia Cristóvão-Ferreira, and Joaquim A. Ribeiro vii viii Contents 8 Astrocytic ATP Release ........................................................................... 157 Dustin J. Hines and Philip G. Haydon 9 Role of Striatal A Receptor Subpopulations 2A in Neurological Disorders ....................................................................... 179 Sergi Ferré, César Quiroz, Marco Orrú, Xavier Guitart, Seema Gulyani, Richard Allen, and Christopher J. Earley Part III Adenosine Function and Dysfunction in Brain Health and Disease 10 Sleep and Adenosine: Human Studies ................................................... 201 Tarja Porkka-Heiskanen 11 Adenosine and Other Purinergic Products in Circadian Timing ................................................................................ 213 Christine Muheim and Steven A. Brown 12 Adenosine in the Immune System .......................................................... 233 György Haskó, Balázs Koscsó, and Balázs Csóka 13 The Bioenergetic Network of Adenosine in Hibernation, Sleep, and Thermoregulation ................................................................. 253 Kelly L. Drew and Tulasi R. Jinka 14 Adenosine and Stroke ............................................................................. 273 Felicita Pedata, Anna Maria Pugliese, Francesca Corti, and Alessia Melani 15 The Many Roles of Adenosine in Traumatic Brain Injury .................. 307 Patrick M. Kochanek, Jonathan D. Verrier, Amy K. Wagner, and Edwin K. Jackson 16 Therapeutic Perspectives of Adenosine Receptor Compounds in Functional Restitution After Spinal Cord Injury ............................ 323 Kwaku D. Nantwi 17 Adenosine and Pain ................................................................................. 343 Jana Sawynok 18 Symptomatic and Neuroprotective Effects of A Receptor 2A Antagonists in Parkinson’s Disease ....................................................... 361 Annalisa Pinna, Nicola Simola, Lucia Frau, and Micaela Morelli 19 Adenosine Receptors and Alzheimer’s Disease .................................... 385 David Blum, Ursula Sandau, Cyril Laurent, Vânia Batalha, Antoine Leboucher, Malika Hamdane, Florence Pasquier, Detlev Boison, Luc Buée, and Luísa V. Lopes Contents ix 20 Adenosine Receptors in Huntington’s Disease ..................................... 409 David Blum, Alberto Martire, Sylvie Burnouf, Bernard Sablonnière, Pierre Krystkowiak, Catherine Ledent, Luisa V. Lopes, and Patrizia Popoli 21 Adenosine and Multiple Sclerosis .......................................................... 435 María Victoria Sánchez-Gómez, Estibaliz González-Fernández, Rogelio O. Arellano, and Carlos Matute 22 Adenosinergic Perspectives on Schizophrenia: Opportunity for an Integrative Synthesis ................................................................... 459 Benjamin K. Yee, Philipp Singer, and Detlev Boison 23 The Role of Adenosine in the Ventral Striatal Circuits Regulating Behavioral Activation and Effort-Related Decision Making: Importance for Normal and Pathological Aspects of Motivation ............................................................................. 493 John D. Salamone, Merce Correa, Patrick A. Randall, Eric J. Nunes, Marta Pardo, and Laura Lopez-Cruz 24 Adenosine and Autism: Physiological Symptoms and Metabolic Opportunities ................................................................. 513 Julia Svedova, Inge-Marie Eigsti, and Susan A. Masino 25 Stress, Brain Adenosine Signaling, and Fatigue-Related Behavioral Processes ............................................................................... 535 Traci N. Plumb, Sarah R. Sterlace, Kelly A. Cavanaugh, and Thomas R. Minor Part IV Adenosine-Based Therapies 26 Disruption of Adenosine Homeostasis in Epilepsy and Therapeutic Adenosine Augmentation .......................................... 561 Detlev Boison 27 Ketogenic Diet and Epilepsy: The Role of Adenosine .......................... 581 Jong M. Rho, Beth Zupec-Kania, and Susan A. Masino 28 Silk: A Biocompatible and Biodegradable Biopolymer for Therapeutic Adenosine Delivery ...................................................... 599 Eleanor M. Pritchard, Detlev Boison, and David L. Kaplan 29 Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy ..................................................... 621 Zsolt Kovács and Arpád Dobolyi Index ................................................................................................................. 657