Hypocretins

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 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

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.

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.

"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.

This issue of Current Topics in Behavioral Neuroscience focuses on the neuropeptide orexin (hypocretin) and brings together scientists from around the world who will provide a timely discussion of how this peptide regulates behavior. This is a fast-moving field, and with the incorporation of novel technologies, new breakthroughs are likely to continue. For example, the use of optogenetic approaches has enabled the identification of the role of orexin-containing neurons in arousal states, critical for higher order functioning. From a clinical perspective, genetic polymorphisms in hypocretin/orexin and orexin receptors are implicated in a number of psychiatric disorders. In addition, advanced clinical trials are currently underway for orexin receptor antagonists in the treatment of insomnia and sleep disorders. We aim to capture a broad audience of basic scientists and clinicians.

The Zebrafish in Biomedical Research: Biology, Husbandry, Diseases, and Research Applications is a comprehensive work that fulfills a critical need for a thorough compilation of information on this species. The text provides significant updates for working vivarium professionals maintaining zebrafish colonies, veterinarians responsible for their care and well-being, zoologists and ethologists studying the species, and investigators using the species to gain critical insights into human physiology and disease. As the zebrafish has become an important model organism for the study of vertebrate development and disease, organ function, behavior, toxicology, cancer, and drug discovery, this book presents an important resource for future research. Presents a complete view of the zebrafish, covering their biology, husbandry, diseases and research applications Includes the work of world-renowned authors Provides the first authoritative and comprehensive treatment of zebrafish in biomedical research as part of the ACLAM series

Peptides play a crucial role in many physiological processes including actions as neurotransmitters, hormones, and antibiotics. Research has shown their importance in such fields as neuroscience, immunology, pharmacology, and cell biology. The Handbook of Biologically Active Peptides presents, for the first time, this tremendous body of knowledge in the field of biologically active peptides in one single reference. The section editors and contributors represent some of the most sophisticated and distinguished scientists working in basic sciences and clinical medicine. The Handbook of Biologically Active Peptides is a definitive, all-encompassing reference that will be indispensable for individuals ranging from peptide researchers, to biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and to endocrinologists. Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas with which they would not ordinarily be familiar. *Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas that they would not ordinarily be familiar. *Fascinating relationships described in the book include the presence of some peptides originally found in frog skin that persist in the human human and brain where they can affect food intake and obesity.