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The Orexin/Hypocretin System

The Orexin/Hypocretin System
Physiology and Pathophysiology

by Seiji Nishino,Takeshi Sakurai

  • Publisher : Springer Science & Business Media
  • Release : 2007-11-22
  • Pages : 416
  • ISBN : 1592599508
  • Language : En, Es, Fr & De
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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 Orexin/Hypocretin System

The Orexin/Hypocretin System
Functional Roles and Therapeutic Potential

by Jim R. Fadel,Joshua A. Burk

  • Publisher : Academic Press
  • Release : 2019-01-03
  • Pages : 188
  • ISBN : 0128137525
  • Language : En, Es, Fr & De
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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 Orexin/hypocretin System

The Orexin/hypocretin System
A Book

by Anantha Shekhar

  • Publisher : Elsevier
  • Release : 2012
  • Pages : 196
  • ISBN : 0444594892
  • Language : En, Es, Fr & De
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"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.

The Role of the Orexin/hypocretin System in the Incubation of Alcohol Craving in Rats

The Role of the Orexin/hypocretin System in the Incubation of Alcohol Craving in Rats
A Book

by Olivia Gilman Mallari

  • Publisher : Unknown Publisher
  • Release : 2016
  • Pages : 73
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Involvement of the Orexin/hypocretin System in Ethanol-conditioned Behavior

Involvement of the Orexin/hypocretin System in Ethanol-conditioned Behavior
A Thesis

by Charlene M. Voorhees

  • Publisher : Unknown Publisher
  • Release : 2009
  • Pages : 50
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Neural Circuit Modelling of the Orexin/Hypocretin System with Implications for Clinical Depression

Neural Circuit Modelling of the Orexin/Hypocretin System with Implications for Clinical Depression
A Book

by Alok Joshi

  • Publisher : Unknown Publisher
  • Release : 2014
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The Orexin System. Basic Science and Role in Sleep Pathology

The Orexin System. Basic Science and Role in Sleep Pathology
A Book

by M.A. Steiner,M. Yanagisawa,M. Clozel

  • Publisher : Karger Medical and Scientific Publishers
  • Release : 2021-05-28
  • Pages : 154
  • ISBN : 3318068446
  • Language : En, Es, Fr & De
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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.

Behavioral Neuroscience of Orexin/Hypocretin

Behavioral Neuroscience of Orexin/Hypocretin
A Book

by Andrew J Lawrence,Luis de Lecea

  • Publisher : Springer
  • Release : 2017-05-29
  • Pages : 322
  • ISBN : 331957535X
  • Language : En, Es, Fr & De
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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.

Hypocretins

Hypocretins
Integrators of Physiological Signals

by Luis De Lecea,J. Gregor Sutcliffe

  • Publisher : Springer Science & Business Media
  • Release : 2007-04-25
  • Pages : 441
  • ISBN : 0387254463
  • Language : En, Es, Fr & De
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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.

Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists

Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists

by Michel Alexander Steiner,Christopher J Winrow

  • Publisher : Frontiers E-books
  • Release : 2014-11-11
  • Pages : 129
  • ISBN : 2889193306
  • Language : En, Es, Fr & De
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Orexin/hypocretin neuropeptides, produced by a few thousand neurons in the lateral hypothalamus, are of critical importance for the control of vigilance and arousal of vertebrates, from fish to amphibians, birds and mammals. Two orexin peptides, called orexin-A and orexin-B, exist in mammals. They bind with different affinities to two distinct, widely distributed, excitatory G-protein- coupled receptors, orexin receptor type 1 and type 2 (OXR-1/2). The discovery of an OXR mutation causing canine narcolepsy, the narcolepsy-like phenotype of orexin peptide knockout mice, and the orexin neuron loss associated with human narcoleptic patients laid the foundation for the discovery of small molecule OXR antagonists as novel treatments for sleep disorders. Proof of concept studies from Glaxo Smith Kline, Actelion Pharmaceuticals Ltd. and Merck have now consistently demonstrated the efficacy of dual OXR antagonists (DORAs) in promoting sleep in rodents, dogs, non-human primates and humans. Some of these antagonists have completed late stage clinical testing in primary insomnia. Orexin drug discovery programs have also been initiated by other large pharmaceutical companies including Hoffmann La Roche, Novartis, Eli Lilly and Johnson & Johnson. Orexins are increasingly recognized for orchestrating the activity of the organism’s arousal system with appetite, reward and stress processing pathways. Therefore, in addition to models of insomnia, pharmacological effects of DORAs have begun to be investigated in rodent models of addiction, depression and anxiety. The first clinical trials in diabetic neuropathy, migraine and depression have been initiated with Merck’s MK-6096 (www.clinicaltrials.gov). Whereas the pharmacology of DORAs is established for their effects on wakefulness, pharmacological effects of selective OXR-1 or OXR-2 antagonists (SORAs) have remained less clear. From an evolutionary point of view, the OXR-2 was expressed first in most vertebrate lineages, whereas the OXR-1 is believed to result from a gene duplication event, when mammals emerged. Yet, both receptors do not have redundant function. Their brain expression pattern, their intracellular signaling, as well as their affinity for orexin-A and orexin-B differs. During the past decade most preclinical research on selective OXR-1 antagonism was performed with SB-334867. Only in recent years, other selective OXR-1 and OXR-2 antagonists with optimized selectivity profiles and pharmacokinetic properties have been discovered, and phenotypes of OXR-1 and OXR-2 knockout mice were described. The present Research Topic (referred to in the Editorial as “special topics issue”) comprises submissions of original research manuscripts as well as reviews, directed towards the neuropharmacology of OXR antagonists. The submissions are preclinical papers dealing with dual and/or selective OXR antagonists that shed light on the differential contribution of endogenous orexin signaling through both OXRs for cellular, physiological and behavioral processes. Some manuscripts also report on convergence or divergence of DORA vs. SORA effects with phenotypes expressed by OXR-1 or OXR-2 knockout animals. Ultimately these findings may help further define the potential of DORAs and SORAs in particular therapeutic areas in insomnia and beyond insomnia.

Orexin and Sleep

Orexin and Sleep
Molecular, Functional and Clinical Aspects

by Takeshi Sakurai,S.R. Pandi-Perumal,Jaime M. Monti

  • Publisher : Springer
  • Release : 2015-09-22
  • Pages : 410
  • ISBN : 3319230786
  • Language : En, Es, Fr & De
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This volume is intended for neuropharmacologists, psychopharmacologists, pharmacologists, pharmacists, sleep researchers, translational neuroscience researchers, and other basic researchers and clinical scientists interested in an interdisciplinary approach to sleep medicine. The level of the book is aiming at CNS researchers, drug development scientists, basic and clinical sleep researchers, as well as senior medical students and fellows in psychiatry and neurology. Orexin and Sleep provides a unique resource, giving a comprehensive and highly readable summary of the basic concepts in orexin biology and pharmacology along with clinical applications in sleep medicine in general, and narcolepsy in particular.

Orexin/Hypocretin System

Orexin/Hypocretin System
A Book

by Anonim

  • Publisher : Elsevier
  • Release : 2012-11-27
  • Pages : 208
  • ISBN : 0444594906
  • Language : En, Es, Fr & De
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Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research. Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered. All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist. Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist

Sleep Hormones

Sleep Hormones
A Book

by Anonim

  • Publisher : Academic Press
  • Release : 2012-05-25
  • Pages : 464
  • ISBN : 0123948398
  • Language : En, Es, Fr & De
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First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines. This volume focuses on sleep hormones. Contributions from leading authorities Informs and updates on all the latest developments in the field

Involvement of the Hypocretin/orexin System in the Addictive Properties of Nicotine

Involvement of the Hypocretin/orexin System in the Addictive Properties of Nicotine
A Book

by Ainhoa Plaza-Zabala

  • Publisher : Unknown Publisher
  • Release : 2012
  • Pages : 347
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Hypocretin-1 and hypocretin-2, also known as orexin-A and orexin-B, are 2 neuropeptides that are exclusively expressed by a small subset of neurons of the lateral hypothalamic area. Despite their restricted expression pattern, hypocretin-containing axons project widely throughout the brain and exert their physiological functions acting on 2 G protein coupled receptors, hypocretin/orexin receptor-1 and hypocretin/orexin receptor-2. Initially, the hypocretin system was related to the regulation of sleep/wake cycles and feeding behavior. Nevertheless, a growing body of evidence has accumulated over the last decade indicating a role for these neuropeptides in drug addiction. In the present thesis, we have evaluated the involvement of hypocretin transmission in the addictive properties of nicotine, the main psychoactive component that sustains tobacco addiction, by using behavioral and biochemical approaches. Our results indicate that hypocretin peptides, mainly through their actions upon hypocretin receptor-1, influence the severity of nicotine withdrawal and modulate the relapse to nicotine-seeking after prolonged periods of abstinence. Given the importance of withdrawal and relapse on the pathophysiology of nicotine addiction, we propose hypocretin receptor-1 as a promising therapeutic target for the development of novel smoking cessation therapies.

Effects of Nicotine on Attention

Effects of Nicotine on Attention
Role of Orexin-1 Receptors

by Stacy Pitcairn

  • Publisher : Unknown Publisher
  • Release : 2020
  • Pages : 25
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The orexin (also called hypocretin) system projects to a wide array of brain regions and is activated by drugs of abuse. The orexin system is best known for its function in wakefulness and arousal, but recent research has suggested that orexins play a vital role in attentional processing. The orexin-1 receptor has been implicated in crucial mechanisms of attention, specifically the transmission of acetylcholine to the cortex. Nicotine is a commonly administered psychoactive drug that has been shown to have cognitive-enhancing effects. Nicotine appears to target the orexin system, suggesting a potential role of the orexin system in mediating the cognitive enhancing effects seen with nicotine. However, the role of orexinergic function in the attentional-promoting effects of nicotine has not been fully described. The present study was designed with two goals in mind: 1) to identify a nicotine dose that improves rat performance in a sustained-attention task and 2) to examine the effect of chronic nicotine administration in conjunction with a selective orexin-1 antagonist, SB-334867, in rats in a sustained-attention task. The results of these experiments suggest that acute nicotine administration impairs attentional functioning, and that chronic nicotine administration slightly improves performance in the sustained-attentional task. Administration of chronic nicotine with SB-334867 blocks the beneficial effect of chronic nicotine in the sustained-attention task. Although these data are preliminary, the findings of this study could provide a novel target that mimics nicotine-induced cognitive activation and give insight into the behavioral and attentional effects of nicotinic activation and orexin-1 antagonism.

A Mathematical Model of Sleep-wake Cycles: the Role of Hypocretin/orexin in Homeostatic Regulation and Thalamic Synchronization

A Mathematical Model of Sleep-wake Cycles: the Role of Hypocretin/orexin in Homeostatic Regulation and Thalamic Synchronization
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2010
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Sleep is vital to our health and well-being. Yet, we do not have answers to such fundamental questions as "why do we sleep?" and "what are the mechanisms of sleep regulation?". Better understanding of these issues can open new perspectives not only in basic neurophysiology but also in different pathological conditions that are going along with sleep disorders and/or disturbances of sleep, e.g. in mental or neurological diseases. A generally accepted concept that explains regulation of sleep was proposed in 1982 by Alexander Borbþely. It postulates that sleep-wake transitions result from the interaction between a circadian and a homeostatic sleep processes. The circadian process is ascribed to a "genetic clock" in the neurons of the suprachiasmatic nucleus of the hypothalamus. The mechanisms of the homeostatic process are still unclear. In this study a novel concept of hypocretin (orexin) - based control of sleep homeostasis is presented. The neuropeptide hypocretin is a synaptic co-transmitter of neurons in the lateral hypothalamus. It was discovered in 1998 independently by two different groups, therefore, obtaining two names, hypocretin and orexin. This neuropeptide is required to maintain wakefulness. Dysfunction in the hypocretin system leads to the sleep disorder narcolepsy, which, among other symptoms, is characterized by severe disturbances of sleep-wake cycles with sudden sleep-attacks in the wake period and interruptions of the sleep phase. On the other hand injection of hypocretin promotes wakefulness and improves the performance of sleep deprived subjects. The major proposals of the present study are the following: 1) the homeostatic regulation of sleep depends on the dynamics of a neuropeptide hypocretin; 2) ongoing impulse generation of the hypocretin neurons during wakefulness is sustained by reciprocal excitatory connections with other neurons, including local glutamate interneurons; 3) the transition to a silent state (sleep) is going along with an a.

Sleep and Movement Disorders

Sleep and Movement Disorders
A Book

by Sudhansu Chokroverty,Richard P. Allen,Arthur S. Walters,Pasquale Montagna

  • Publisher : Oxford University Press
  • Release : 2012-04-01
  • Pages : 624
  • ISBN : 0199795231
  • Language : En, Es, Fr & De
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Sleep and Movement Disorders is the second edition of a successful book that was the first of its kind. Since its publication in 2002, significant progress has been made in our understanding of motor control in sleep and the relationship between sleep and movement disorders. Each editor is an authority on the subject and has assembled expert specialists for their chapter authors. The topic is very timely, the latest edition of the International classification of sleep disorders (ICSD-2, 2005) included a separate category of 'Sleep Related Movement Disorders' emphasizing the increasing awareness of sleep-related movements and the importance of recognizing sleep-related movement disorders for diagnosis, differential diagnosis and treatment. This is a comprehensive resource, including all findings from the last 8 years of research. All the previous chapters have been revised with new materials and references. Several chapters have been added to address recent advances. For instance, new sleep-related disorders have been classified and diagnosed, including catathrenia, alternating leg muscle activation (ALMA), propriospinal myoclonus (PSM) at sleep onset, faciomandibular myoclonus at sleep onset, etc. Further understanding of the pathophysiology of RLS-PLMS is addresses, as is the neurobiology of REM Behavior Disorder (RBD), predictors of neurodegenerative diseases, and so on. Sleep and Movement Disorders is divided into four major sections and subsections preceded by an introductory essay to provide perspective on the subject. The book is intended for all sleep and movement disorders specialists as well as those neurologists, internists including pulmonologists, psychiatrists, psychologists, otolaryngologists, pediatricians, neurosurgeons, dentists and family physicians who must deal with the many patients suffering from undiagnosed or underdiagnosed sleep disorders including sleep-related abnormal movements.

Integrative Therapies for Depression

Integrative Therapies for Depression
Redefining Models for Assessment, Treatment and Prevention

by James M. Greenblatt,Kelly Brogan

  • Publisher : CRC Press
  • Release : 2015-12-01
  • Pages : 531
  • ISBN : 1498702309
  • Language : En, Es, Fr & De
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Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention summarizes emerging theories and research findings on various nonpharmaceutical therapies to treat mood disorders.Supported by the review of nearly 3000 scientific studies, the book describes the concepts of inflammation, genetics, hormonal imbalance, g

Sleep, An Issue of Clinics in Chest Medicine - E-Book

Sleep, An Issue of Clinics in Chest Medicine - E-Book
A Book

by Teofilo Lee-Chiong, Jr,Vahid Mohsenin,H. Klar Yaggi

  • Publisher : Elsevier Health Sciences
  • Release : 2010-06-14
  • Pages : 392
  • ISBN : 1455706035
  • Language : En, Es, Fr & De
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This issue offers a valuable update in the fast-moving specialty of sleep medicine. Topics covered include: The Neurobiology of Sleep; Adult Obstructive Sleep Apnea; Central Sleep Apnea (including complex sleep apnea and ASV); Pediatric Sleep-Related Breathing Disorders; Hypoventilation Syndromes; Metabolism in OSA; Cardiovascular Consequences of Sleep Apnea; Home Sleep Apnea Testing; Insomnia; Excessive Sleepiness; Narcolepsy; Restless Leg Syndrome and Movement Disorders; Parasomnia; Circadian Rhythm Sleep Disorders; Medication Effects on Sleep; and Polysomnography.

Issues in Brain and Cognition Research: 2013 Edition

Issues in Brain and Cognition Research: 2013 Edition
A Book

by Anonim

  • Publisher : ScholarlyEditions
  • Release : 2013-05-01
  • Pages : 1179
  • ISBN : 1490106154
  • Language : En, Es, Fr & De
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Issues in Brain and Cognition Research / 2013 Edition is a ScholarlyEditions™ book that delivers timely, authoritative, and comprehensive information about Cerebral Blood Flow and Metabolism. The editors have built Issues in Brain and Cognition Research: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Cerebral Blood Flow and Metabolism in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Issues in Brain and Cognition Research: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.