The Orexin Hypocretin System

Book Description :

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

Book Description :

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.

Book Description :

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.

Book Description :

"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.

Book Description :

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.

Book Description :

Download The Role of the Orexin hypocretin System in the Incubation of Alcohol Craving in Rats book written by Olivia Gilman Mallari, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Book Description :

Anxiety and fear are emotions that are vital for individuals when dealing with difficult challenges and threats. However, persistent vigilance and frequent recall of memories associated with a fearful experience can lead to generalized anxiety disorder, posttraumatic stress disorder (PTSD), and phobias. Orexins (hypocretins) are neuropeptides that play a critical role in promoting arousal. Accumulating evidence suggests that orexin neurons are activated in animals exposed to stressful conditions and that orexins are involved in the regulation of anxiety and fear. In this thesis, the role of the orexins in anxiety and fear was studied using behavioral, biochemical, and pharmacological methods. Experiments were done to identify some of the possible mechanisms involved. First, microinjections of orexin peptides (orexin-A and orexin-B) into the paraventricular nucleus of the thalamus (PVT) induced anxiety-like behaviors. The anxiogenic effect produced by microinjections of orexin-A in the PVT was attenuated by blocking receptors for the stress-related peptides, corticotropin-releasing factor (CRF) and dynorphin. Second, the mRNA levels for prepro-orexin (ppOX) and the orexin 1 receptor (OX1R) were found to be increased in the posterior hypothalamus of shocked rats at 2 weeks post-shock. Third, 2 weeks after the footshocks, an enhanced level of CRF mRNA in the amygdala and ppOX mRNA in the posterior hypothalamus were detected in a subset of shocked rats that displayed an acute fear response to a novel tone and that eventually resulted in a generalized anxiety (high responders, HR). Fourth, the dual orexin antagonist TCS1102 (20 mg/kg; i.p.) and OX1R antagonist SB334867 (20 and 30 mg/kg; i.p.) decreased fear level when tested at 2 weeks post-shock. These results suggest that endogenously released orexins regulate anxiety through acting on the PVT and that the brain kappa and CRF systems could be involved. The results also indicate that changes in orexins and CRF occur specifically in HR. These findings provide a better understanding of the brain mechanisms contributing to hyperarousal and anxiety. In addition, the results support the use of orexin receptor antagonists, especially OX1R antagonists, in the treatment of anxiety disorders including PTSD, panic attacks, and phobias.

Book Description :

Download Neural Circuit Modelling of the Orexin Hypocretin System with Implications for Clinical Depression book written by Alok Joshi, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Book Description :

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.

Book Description :

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.

Book Description :

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.

Book Description :

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

Book Description :

The human genome encompasses ˜ 860 G protein-coupled receptors (GPCRs) including 374 non-chemosensory GPCRs. Half of these latter GPCRs recognize (neuro)peptides as natural ligands. GPCRs thus play a pivotal role in neuroendocrine communication. In particular, GPCRs are involved in the neuroendocrine control of feeding behavior, reproduction, growth, hydromineral homeostasis and stress response. GPCRs are also major drug targets and hence possess a strong potential for the development of innovative pharmaceuticals. The aim of this Research Topic was to assemble a series of review articles and original research papers on neuropeptide GPCRs and their ligands that would illustrate the different facets of the studies currently conducted in this domain.

Book Description :

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.

Book Description :

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.

Book Description :

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.

Book Description :

In recent years our understanding of molecular mechanisms of drug action and interindividual variability in drug response has grown enormously. Meanwhile, the practice of anesthesiology has expanded to the preoperative environment and numerous locations outside the OR. Anesthetic Pharmacology: Basic Principles and Clinical Practice, 2nd edition, is an outstanding therapeutic resource in anesthesia and critical care: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology and toxicology of anesthetic drugs. The new Section 4, Therapeutics of Clinical Practice, provides integrated and comparative pharmacology and the practical application of drugs in daily clinical practice. Edited by three highly acclaimed academic anesthetic pharmacologists, with contributions from an international team of experts, and illustrated in full colour, this is a sophisticated, user-friendly resource for all practitioners providing care in the perioperative period.

Book Description :

Fully updated and revised according to student feedback, the sixth edition of Mayo Clinic Medical Neurosciences: Organized by Neurologic System and Level provides a systematic approach to anatomy, physiology, and pathology of the nervous system inspired by the neurologist's approach to solving clinical problems. This volume has 4 sections: 1) an overview of the neurosciences necessary for understanding anatomical localization and pathophysiologic characterization of neurologic disorders; 2) an approach to localizing lesions in the 7 longitudinal systems of the nervous system; 3) an approach to localizing lesions in the 4 horizontal levels of the nervous system; and 4) a collection of clinical problems. This book provides the neuroscience framework to support the neurologist in a clinical setting and is also a great resource for neurology and psychiatry board certifications. This is the perfect guide for all medical students and neurology, psychiatry, and physical medicine residents at early stages of training. New to This Edition - A chapter devoted to multiple-choice questions for self-assessment - Discussion of emerging concepts in molecular, cellular, and system neurosciences - New chapters on emotion and consciousness systems - Incorporation of new discoveries in neuroimaging and an appendix for tables of medications commonly used to treat neurologic disorders

Book Description :

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.

Book Description :

The human hypothalamus, a small structure at the base of the brain, has strategic importance for the harmonic function of the human body. It controls the autonomic nervous system, neuroendocrine function, circadian and circannual rhythms, somatic activities, and behavior, and is situated at the borders between the brain and the body and the brain and the soul, meeting points for mind and body. The hypothalamus is involved in a wide range of higher mental functions, including attention, learning and reinforcement of mnemonic processes, emotional control, mood stability, and cognitive-emotional interactions. It also has a role to play in behavioral disorders, panic reactions, cluster headache, gelastic epilepsy, mental deficiency, periodic disorders, depression, autism, and schizophrenia, and in a substantial number of neurodegenerative diseases. It enlarges greatly the dimensions of the hypothalamic contribution in controlling psychosomatic equilibrium and retaining internal unity of the human existence.