The Orexin/Hypocretin System
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The Orexin/Hypocretin System : Physiology and Pathophysiology

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Orexin/hypocretin research began in 1998, as a result of the discovery of a new hypothalamic neuropeptide. In 1999, it was found that mutations in the orexin/ hypocretin-related genes caused a sleep disorder (narcolepsy) in dogs and mice. These findings were soon followed by the discoveries of orexin/hypocretin ligand deficiency in human narcolepsy. The finding of the major pathophysiological mechanisms of human narcolepsy resulted in its reclassification as a neurological, not a psychiatric, disorder. The - portance of early diagnosis and initiation of treatment for human narcolepsy has been repeatedly emphasized because the disease typically starts around puberty (when social and school influences become important). Orexin/hypocretin de- ciency in narcolepsy subjects can be detected clinically in cerebrospinal fluid (CSF) orexin/hypocretin measures (low CSF orexin/hypocretin levels are strongly asso- ated with narcolepsy-cataplexy among various neurologic and sleep disorders). Thus, the CSF orexin/hypocretin measurements are expected to be included as a diagnostic test for narcolepsy-cataplexy in the second revision of international di- nostic criteria (ICSD). This positive diagnostic test is very useful for establishing an early diagnosis for narcolepsy-cataplexy, and many patients will likely receive im- diate benefits. Cerebrospinal orexin/hypocretin measurements are also informative for the nosological classification of hypersomnia. Because orexin/hypocretin de- ciency is observed in most human narcolepsy-cataplexy, orexin/hypocretin repla- ment therapy is now a promising new choice for the treatment of human narcolepsy, and research in this area is actively in progress.show more

Product details

  • Hardback | 416 pages
  • 184 x 258 x 28mm | 1,079.56g
  • Humana Press Inc.
  • Totowa, NJ, United States
  • English
  • 2005 ed.
  • 9 Illustrations, color; 142 Illustrations, black and white; 416 p. 151 illus., 9 illus. in color.
  • 1588294447
  • 9781588294449

Back cover copy

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.show more

Table of contents

Part I. History History and Overview of Orexin/Hypocretin Research: From Orphan GPCR to Integrative Physiology Michihiro Mieda and Takeshi Sakurai Part II. Overview of the Orexin/Hypocretin Neuronal System Orexin and Orexin Receptors Takeshi Sakurai Orexin Projections and Localization of Orexin Receptors Jacob N. Marcus and Joel K. Elmquist Neuronal Responses to Hypocretin/Orexin Anthony N. van den Pol and Claudio Acuna-Goycolea Afferent System of Orexin Neurons Akihiro Yamanaka Part III. Assessment of Orexin/Hypocretin Functions in Tissue and Biological Fluids Hypocretin Measurements in the CSF, and Blood and Brain Tissue: Basic and Clinical Applications Seiji Nishino Hypocretin Receptor-Activated G Proteins Revealed by [35S]GTPgS Autoradiography Rene Bernard, Ralph Lydic, and Helen A. Baghdoyan Part IV. Physiology A. Orexin/Hypocretin System and Hypothalamic Function Orexin System and Feeding Behavior Takeshi Sakurai Orexins and the Autonomic Nervous System Tetsuro Shirasaka and Masamitsu Nakazato Neuroendocrine Role of the Orexins (Hypocretins) Shahrad Taheri The Orexin/Hypocretin System and Stress and Emotion Yoichi Ueta and Hiroaki Fujihara B. Orexins/Hypocretins and Sleep Regulation Hypocretin as a Wakefulness Regulatory Peptide Luis de Lecea and J. Gregor Sutcliffe Hypocretin/Orexin Tonus and Vigilance Control Yasushi Yoshida and Seiji Nishino Hypocretin System and Aminergic and Cholinergic Systems in the Control of Vigilance Krister S. Eriksson and Helmut L. Haas Orexin and Hypothalamic Control of Sleep and Waking Rodrigo A. Espana and Thomas E. Scammell Hypocretin/Orexin and Motor Function Jerome M. Siegel Part V. Pathophysiology:Narcolepsy and Orexin/Hypocretin Deficiency A. Orexin/Hypocretin Deficiency and Narcolepsy Overview of Human Narcolepsy Scott Fromherz and Emmanuel Mignot Canine Models of Narcolepsy Seiji Nishino Rodent Models of Human Narcolepsy-Cataplexy Michihiro Mieda and Masashi Yanagisawa B. Orexin/Hypocretin Deficiency in Human Narcolepsy and Other Conditions Hypocretin Deficiency in Human Narcolepsy: Mutation Screening, Neuropathology, and CSF Hypocretin-1 Level Patrice Bourgin, Jamie M. Zeitzer, and Emmanuel Mignot Hypocretin Status in Neurological Disorders in Relation to Excessive Sleepiness and Cataplexy Takashi Kanbayashi, Junko Arii, Hideaki Kondo, Tetsuo Shimizu, and Seiji Nishino Hypocretin Measures in Psychiatric Disorders Ronald M. Salomon Neuroendocrinology of Human Narcolepsy Gert Jan Lammers, Sebastiaan Overeem, and Hanno Pijl Narcolepsy and Autoimmunity Shahrad Taheri, Jose Paterno, Ling Lin, and Emmauel Mignot C. Treatment/Pharmacology Pharmacology of Orexin/Hypocretin Peptides and Small Molecules Stephen J. Perry, David A. Schwarz, and Richard A. Maki Rescue of Narcoleptic Orexin Neuron-Ablated Mice by Ectopic Overexpression of Orexin Peptides Michihiro Mieda, Jon T. Willie, and Takeshi Sakurai Hypocretin/Orexin Replacement Therapy in Hypocretin/Orexin-Deficient Narcolepsy: An Overview Nobuhiro Fujiki and Seiji Nishino Indexshow more

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