The orexin system, discovered in 1998, has emerged as a crucial player in regulating the sleep and wake balance inside our brain. This discovery has sparked a burst of novel and dynamic research on the physiology and pathology of sleep. The Orexin System: Basic Science and Role in Sleep Pathology honors this research and the authors share their ideas and perspectives on the novel developments within the field. The book examines the intricate role of the orexin system in regulating sleep and wake, and its interaction with other wake-regulating systems. The orexin system is dissected at the cellular and molecular level to explore the diversity of the orexin-producing neurons, their projections, and their signaling pathways. Additionally, the book discusses the diseases which are associated with a dysfunctional orexin system, such as narcolepsy, insomnia, substance abuse, and Alzheimer’s disease, and explores the new potential therapeutic applications derived from the burst of research around this fascinating system. This publication is essential reading for neurobiologists, neurologists, psychopharmacologists, sleep researchers, and other researchers and clinical scientists interested in sleep, sleep research, insomnia, and medicine in general.

The first report that rapid eye movements occur in sleep in humans was published in 1953. The research journey from this point to the realization that sleep consists of two entirely independent states of being (eventually labeled REM sleep and non-REM sleep) was convoluted, but by 1960 the fundamental duality of sleep was well established including the description of REM sleep in cats associated with “wide awake” EEG patterns and EMG suppression. The first report linking REM sleep to a pathology occurred in 1961 and a clear association of sleep onset REM periods, cataplexy, hypnagogic hallucinations and sleep paralysis was fully established by 1966. When a naïve individual happens to observe a full-blown cataplexy attack, it is both dramatic and unnerving. Usually the observer assumes that the loss of muscle tone represents syncope or seizure. In order to educate health professionals and the general public, Christian Guilleminault and I made movies of full-blown cataplectic episodes (not an easy task). We showed these movies of cataplexy attacks to a number of professional audiences, and were eventually rewarded with the report of a similar abrupt loss of muscle tone in a dog. We were able to bring the dog to Stanford University and with this as the trigger, we were able to develop the Stanford Canine Narcolepsy Colony. Breeding studies revealed the genetic determinants of canine narcolepsy, an autosomal recessive gene we termed canarc1. Emmanuel Mignot took over the colony in 1986 and began sequencing DNA, finally isolating canarc1 in 1999.

The Orexins/Hypocretins System: Functional Roles and Therapeutic Potential summarizes research on both the physiological functioning of orexins, their impact on homeostatic processes, and related disorders. The book encompasses the effects on appetite, sleep, substance abuse, cognition, and anxiety. Additionally, it examines new therapeutic approaches utilizing orexins, including utilization of orexin receptors for drug development. It is essential reading for neuroscience researchers interested in brain-behavior relationships, as well as psychiatrists, endocrinologists and pharmacologists. - Provides an overview of new research on orexins/hypocretins - Includes an overview of intracellular signaling and orexin physiology - Discusses the effects on arousal, appetite, cognition, addiction and anxiety - Examines orexin based therapies and their potential use in disorders - Explores orexin receptors for drug development

"In The Orexin/Hypocretin System: Physiology and Pathophysiology, leading researchers and clinicians set the stage for further research on the loss of orexin/hypocretin neurons in humans, regulation of sleep and wakefulness by the orexin/hypocretin system, and the role of the orexin/hypocretin system in many other physiological processes, including feeding, autonomic regulation, and neuroendocrine regulation. Topics of interest include an assessment of the functions and the physiology of orexin/hypocretin, its pathophysiology in human narcolepsy-cataplexy, and possible pharmacological treatments. The authors also introduce several experimental methods for orexin/hypocretin research, and, using multidisciplinary approaches, explain their uses and limitations." "Authoritative and state-of-the-art, The Orexin/Hypocretin System: Physiology and Pathophysiology will aid scientists in the search for novel bioactive peptides and their receptors, as well as novel physiological insights and opportunities for the clinical treatment of not only narcolepsy, but also a broad range of diseases associated with endocrine, feeding and body weight regulation."--Résumé de l'éditeur.

Impairment of orexin/hypocretin signaling causes narcolepsy-cataplexy in animals and humans. Most human narcolepsy-cataplexy cases are associated with orexin/hypocretin ligand deficiency, which can be detected clinically using cerebrospinal orexin/hypocretin measures and may lead to future treatments with orexin/hypocretin replacement therapy. In The Orexin/Hypocretin System: Physiology and Pathophysiology, leading researchers and clinicians review these exciting developments to set the stage for further research on the loss of orexin/hypocretin neurons in humans, regulation of sleep and wakefulness by the orexin/hypocretin system, and the role of the orexin/hypocretin system in many other physiological processes, including feeding, autonomic regulation, and neuroendocrine regulation. Topics of interest include an assessment of the functions and the physiology of orexin/hypocretin, its pathophysiology in human narcolepsy-cataplexy, and possible pharmacological treatments. The authors also introduce several experimental methods for orexin/hypocretin research, and, using multidisciplinary approaches, explain their uses and limitations. Authoritative and state-of-the-art, The Orexin/Hypocretin System: Physiology and Pathophysiology will aid scientists in the search for novel bioactive peptides and their receptors, as well as novel physiological insights and opportunities for the clinical treatment of not only narcolepsy, but also a broad range of diseases associated with endocrine, feeding, and body weight regulation.

The field of narcolepsy has developed enormously within the last 10 years. Indeed the understanding of the basics of sleep-wake regulation and the discovery of new neurotransmitter systems (the hypocretins) has boosted research and key findings in the field, providing important insights into how sleep is regulated. Consequently narcolepsy now receives a great deal of attention from both clinicians and scientists throughout the world. Narcolepsy: Pathophysiology, Diagnosis, and Treatment not only offers an engaging and comprehensive treatment of a fascinating disorder but also includes a DVD that offers a unique and large collection of movies displaying the symptoms of narcolepsy in people and animals. Written by some of the best experts in the field, the book focuses on the pathophysiology of the problem and also provides critical, up-to-date insights on the key clinical issues: how to diagnose the disorder, how to treat it, and how to best manage psychosocial problems. The first and only guide to span the latest advances in narcolepsy, this reference provides sections in etiology, neurochemistry, the role of the hypocretins in sleep-wake regulation, animal models in narcolepsy, the key role of the hypothalamus, REM-sleep dysregulation, diagnosis and classification, and treatment. Compiled by an international group of more than 30 authors, Narcolepsy: Pathophysiology, Diagnosis, and Treatment is an indispensable resource for all clinicians and scientists with an interest in narcolepsy.

The first comprehensive book on the subject, The Genetic Basis of Sleep and Sleep Disorders covers detailed reviews of the general principles of genetics and genetic techniques in the study of sleep and sleep disorders. The book contains sections on the genetics of circadian rhythms, of normal sleep and wake states and of sleep homeostasis. There are also sections discussing the role of genetics in the understanding of insomnias, hypersomnias including narcolepsy, parasomnias and sleep-related movement disorders. The final chapter highlights the use of gene therapy in sleep disorders. Written by genetic experts and sleep specialists from around the world, the book is up to date and geared specifically to the needs of both researchers and clinicians with an interest in sleep medicine. This book will be an invaluable resource for sleep specialists, neurologists, geneticists, psychiatrists and psychologists.

Narcolepsy serves as a prototype of how the interaction of high quality clinical research and groundbreaking basic science can collaborate to defne the cause of a disease and change forever how we evaluate and treat it. There is scarcely a topic in this book that would have been covered in the same way 10 years ago as it is d- cussed today. We are also fortunate that many of the players in this dramatic tu- around have contributed to this volume, so that the result is a tapestry of the events that have transformed the feld over the last decade that is both authentic and detailed. The frst section of the book provides much of the basic science background. As described in the frst two chapters, the dramatic convergence of lines of evidence from two different laboratories frst demonstrated in 1999 that narcolepsy is a disease of loss of neurotransmission by lateral hypothalamic neurons making the peptides that have been called orexins or hypocretins. These fndings did much to clarify and unify a feld that had puzzled for decades over the fundamental nature of this puzzling disease, as refected in the chapters that review its epidemiology and neuroanatomical and imaging fndings.

The three different types of muscle tissue found in the animal kingdom are cardiac, skeletal, and smooth. The muscle cells are not only complex but also fascinating. In recent years there has been substantial advances in our understanding of muscle cell biology, especially in areas of molecular anatomy, basic physiology, understanding disease mechanisms, and therapeutic targets. Consequently, this book mainly focuses not only on the biology of myocytes, but also on all-encompassing disciplines pertaining to muscle tissue, such as fundamental physiology, molecular mechanisms of diseases, muscle regeneration, etc. for all three types of muscle, namely, skeletal, cardiac, and smooth muscle. As a result, the goal of this book is to consolidate the recent advances in the area of muscle biology/diseases/regeneration covering a broad range of interrelated topics in a timely fashion and to disseminate that knowledge in a lucid way to a greater scientific audience. This book will prove highly useful for students, researchers, and clinicians in muscle cell biology, exercise physiology/science, stem cell biology, developmental biology, cancer biology, pathology, oncology, as well as tissue engineering and regenerative medicine. This quick reference will benefit anyone desiring a thorough knowledge pertaining to recent advances in muscle biology in the context of health and disease.

An up-to-date, superbly illustrated practical guide to the effective use of neuroimaging in the patient with sleep disorders. The only book to date to provide comprehensive coverage of this topic. A must for all healthcare workers interested in understanding the causes, consequences and treatment of sleep disorders.