Main description:

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.

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

Index