This is a comprehensive reference book on an essential mitochondrial enzyme, cytochrome c oxidase (COX) - the culmination of four decades of work. This enzyme's biochemical activity originated and evolved more than a billion years ago. Nevertheless, its contributions to the function of neurons remains relatively obscure. COX is not just a housekeeping enzyme engaged in energy generation, but a treasure trove for the discovery of numerous neuronal properties chronicled in this book. Various methods of studying COX in neurons are described, including biochemistry, histochemistry, cytochemistry, immunohistochemistry, in situ hybridization, and gene isolation. These methods revealed that COX also plays a critical role in rescuing the metabolic integrity of neurons exposed to toxins. The goal of this book is to raise the curiosity of readers to this invaluable enzyme so researchers will continue the quest to uncover neuronal properties unveiled by this enzyme.
Rezensionen / Stimmen
"Your book is clearly written and very useful, especially as a reference for the roles of transcription factors and genetic defects."
John M. Allman, Ph.D., Frank P. Hixton Professor of Neurobiology, Caltech
"This book offers a compelling account of a scientific journey that spans from neuroanatomy to the intricate molecular mechanisms underlying neuronal processing. I highly recommend it to aspiring biomedical students. For those drawn to neuroscience, it introduces bioenergetics as a powerful investigative tool. And for those already interested in bioenergetics, it reveals the brain as a fascinating and rich field of study. A truly enlightening read that bridges two dynamic areas of biomedical science."
Yidong Bai, Ph.D., Professor, Department of Cell Systems and Anatomy, University of Texas Health San Antonio
"This book offers valuable insights into neuroscience and bioenergetics, highlighting the role of cytochrome c oxidase in cellular respiration and neuronal function. The well-organized chapters provide accessible yet detailed explorations of molecular pathways, linking transcriptional regulation, neuronal activity, and energy metabolism. This authoritative resource is essential for neuroscientists, molecular biologists, and students in these fields."
Shilpa S. Dhar, Ph.D., Assistant Professor of GI Medical Oncology, University of Texas MD Anderson Cancer Care Center
"This is great! I learned so much! I think it's safe to say your research has made an impact, and it's truly impressive when it's gathered all in one place like this."
Serena Dudek Sommer, Ph.D.
"This is an extremely impressive body of work that is so well explained with the known details and caveats. The frequent summary interpretations are a big help to the readers. Congratulations on your many stunning findings and this masterful compilation of science."
Carol A. Everson, Ph.D., Professor of Medicine, Medical College of Wisconsin
"Your book is an incredible book of great importance."
Francisco Gonzalez-Lima, Ph.D., George I. Sanchez Centennial Professor of Psychology, The University of Texas at Austin
"The whole book looks really interesting."
Lawrence I. Grossman, Ph.D., Henry L. Brasza Professor of Molecular Medicine and Genetics, Director of Center for Molecular Medicine and Genetics, Wayne Satte University
"I enjoyed the book very much... I think it is a fantastic contribution to the literature. As always, your writing is so clear and precise that it makes the complex subject material understandable with no loss of detail. I enjoyed reading it all, and especially, catching up on the upstream regulators of COX."
Robert F. Hevner, Ph.D., Professor of Neuropathology, University of California, San Diego
"This book provides a comprehensive overview of cytochrome oxidase and beautifully integrates studies of the enzyme at neurofunctional, developmental, biochemical, genetic, and clinical levels. It is very readable and will provide a valuable resource for the next generation of scientists, putting a trove of useful knowledge all in one place right in their hands. That was your goal and you have achieved it."
Jonathan C. Horton M.D., Ph.D., William F. Hoyt Professor of Ophthalmology, Neuroscience Program, UCSF
"It is a wonderful book, and of course very well illustrated. The preface is excellent.... What a powerful new agent. Chapter 1 is good, and it should come first. Chapter 2 is even better. The Abstract is helpful... chapter 4 .... is very well illustrated .I'm very impressed with what you have done. The chapters are well written and illustrated.... you have produced a wonderful and very impressive book."
Jon Kaas, Ph.D., Distinguished Centennial Professor of Psychology, Member of the US National Academy of Sciences, Vanderbilt University
"Overall, a great job! I especially enjoyed much of the EM and COX histochemistry, beautiful work.
Congratulations!....Your book is a comprehensive, synthesizing review of cytochrome oxidase. It should be very valuable to anyone working in the area; a treasure trove."
Joseph C. LaManna, Ph.D., Jeannette M. and Jospeh S. Silber Professor Emeritus of Physiology, Case Western Reserve University School of Medicine
"The first chapter ... is a great introduction. You have done an amazing job pulling all this information together."
Margaret I. Lomax, Ph.D., Research Professor Emerita, Kresge Research Institute, University of Michigan
"This book is helpful for the Neuroscientists to understand cytochrome oxidase from cell to molecule."
Xuegang Luo, Ph.D., Department of Anatomy and Neurobiology, Xiangya School of Medicine
"I enjoyed reading your book. I learned a lot that I did not know about COX biology....This is a well-written, scholarly book that is really two books."
Henry J. Ralston, III, M.D., Professor and Chair Emeritus, Department of Anatomy, UCSF
"This wonderful and informative book on Cytochrome c Oxidase is written by Margaret Wong-Riley. It contains 18 chapters describing all aspects of this interesting and important enzyme. It also describes how the enzyme was discovered and the subsequent works conducted by the authors and many other scientists on the role of the enzyme in the nervous systems. It is a most useful book for established and young scientists to learn about this topic. I am sure this book will inspire the curiosity of neuroscientists to conduct further work on Cytochrome c Oxidase."
Kwok-Fai So, Ph.D., Director, GHM Institute of CNS Regeneration, Member of Chinese Academy of Sciences, Jinan University
"In the late 1970s Margaret Wong-Riley pioneered the histochemical localization of a metabolic enzyme, cytochrome oxidase, in the mammalian cortex. The levels of this enzyme are dramatically affected by the activity of the neurons that express it, integrated over some period of time. This discovery has given rise among other things to an understanding of the compartmentalization of multiple cortical areas, with nearly 300 papers by many authors on cytochrome oxidase patterns in the visual cortex alone. It has also stimulated the discoveries of additional activity-dependent changes. Her new book is a scholarly summary of the literature on cytochrome oxidase together with an interpretation of how neural activity interacts with it. It will be useful for all students of brain organization."
Michael P. Stryker, Ph.D., William Francis Ganong Professor of Physiology, Kavli Institute for Fundamental Neuroscience
"I would like to congratulate You on this book. It is a very nice contribution to the history of "our enzyme". I am very pleased with the book. ... You have presented the facts in a very readable way, and I hope your book will be published soon so that I can cite it."
Dr. Sebastian Vogt, Professor, Cardiovascular Research Lab for Bioenergetics, Heart Surgery, Phillipps University of Marburg
Margaret Wong-Riley received her BS (1965) and MA (1966) in Science Education from Teachers College, Columbia University, NY and her PhD (1970) in Anatomy/Neuroanatomy from Stanford University, CA. Her postdoctoral research was at the U. of Wisconsin, Madison and at NIH. In 1973, she became an Assi't and later an Assoc. Professor with tenure at UC San Francisco. For family reasons, shemoved to the Medical College of Wisconsin, where she assumed Associate Professorship (1981) followed by full Professorship (1984) until her retirement in 2019. She taught neuroscience to medical and graduate students, and her neuroscience research was funded continuously by NIH for 40 years. Her main focus was the cellular and molecular mechanisms of energy regulation in neurons. She found that cytochrome c oxidase, a mitochondrial enzyme essential for life, is a sensitive and reliable indicator of neuronal activity. The technique that her lab developed has been widely used, and new regions were uncovered in the primate visual cortex. Her lab systematically probed the molecular mechanisms of bigenomic regulation of this enzyme and how it is tightly coupled to the regulation of neurotransmitter receptor genes in neurons. They also found that cytochrome c oxidase plays a critical role in photobiomodulationthat rescued the metabolic integrity of neurons exposed to various toxins. Another major revelation pertains to the critical period of postnatal development in both the respiratory system and the primary visual cortex. An abrupt and significant fall in cytochrome oxidase level during this time was correlated with unexpected changes in neurotransmitter receptor expressions and electrophysiological properties of neurons. Thus far, she has published 167 research articles, 15 book chapters, and edited a book, "Neuroscience Secrets" (2000, Hanley & Belfus; translated also into Spanish and Portuguese). She served on many NIH review panels and Study Sections as well as a number of editorial boards. She became the Founding Editor-in-chief of Eye and Brain in 2010. In 1996, she was honored with the Roy and Sherrington Award given by the Gordon Research Conference at Oxford
Chapter 1: Introduction: Cytochrome c oxidase.
Chapter 2: A sensitive indicator of metabolic plasticity in neurons.
Chapter 3: The entire neuron is not metabolically homogeneous: importance of dendrites.
Chapter 4: Uncovering a new region in the supragranular layers of the primate visual cortex: puffs, patches, blobs or dots.
Chapter 5: Not all neurons respond alike to the same functional insult.
Chapter 6: Methods for analyzing COX: histochemistry, cytochemistry, generation of antibodies and immunohistochemistry, biochemistry, and molecular biological techniques.
Chapter 7: Role of cytochrome c oxidase in photobiomodulation.
Chapter 8: Molecular mechanisms of regulating the bigenomic cytochrome c oxidase in neurons.
Chapter 9: Nuclear respiratory factor 1 (NRF-1) regulates COX in neurons.
Chapter 10: Nuclear respiratory factor 2 (NRF-2) regulates COX in neurons.
Chapter 11: Specificity protein 4 (Sp4) regulates COX in neurons.
Chapter 12: Peroxisome proliferator-activated receptor-? coactivator 1? (PGC-1?) in neurons.
Chapter 13: Tight coupling of neuronal activity and energy metabolism at the transcriptional level.
Chapter 14: Critical period of brain stem respiratory system in rats.
Chapter 15: Critical period of primary visual cortex in rats.
Chapter 16: Role of cytochrome c oxidase in Alzheimer's Disease and other neurodegenerative disorders.
Epilogue: Open questions.
