The Orexin/Hypocretin System: Physiology and Pathophysiology

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Seiji Nishino, Takeshi Sakurai
Springer Science & Business Media, Nov 22, 2007 - Medical - 416 pages
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This cutting-edge review of the orexin/hypocretin system sets the stage for advanced research on the pathological mechanisms underlying 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. The authors also introduce several experimental methods for orexin/hypocretin research, and, using multidisciplinary approaches, explain their uses and limitations. Contents: Part I. History. History and Overview of Orexin/Hypocretin Research: From Orphan GPCR to Integrative Physiology. Part II. Overview of the Orexin/Hypocretin Neuronal System. Orexin and Orexin Receptors. Orexin Projections and Localization of Orexin Receptors. Neural Responses to Hypocretin/Orexin. Afferent Systems of Orexin Neurons. Part III. Assessment of Orexins/Hypocretin Functions in Tissue and Biological Fluids. Hypocretin Measurements in the CSF, Blood, and Brain Tissues: Basic and Clinical Applications. Hypocretin Receptor-Activated G Proteins Revealed by [35S]GTPgS Autoradiography. Part IV. Physiology. A. Orexin/Hypocretin System and Hypothalamic Function. Orexin System and Feeding Behavior. Orexins and the Autonomic Nervous System. Neuroendocrine Role of the Orexins (Hypocretins). Orexin/Hypocretin System and Stress and Emotion. B. Orexins/Hypocretins and Sleep Regulation. Hypocretin as a Wakefulness Regulatory Peptide. Hypocretin/Orexin Tonus and Vigilance Control. Hypocretin System and Aminergic and Cholinergic Systems in the Control of Vigilance. Orexin and Hypothalamic Control of Sleep and Waking. Hypocretin/Orexin and Motor Function. Part V. Pathophysiology: Narcolepsy and Orexin/Hypocretin Deficiency. A Orexin/Hypocretin Deficiency and Narcolpesy. Overview of Human Narcolepsy. Canine Models of Narcolepsy. Rodent Models of Human Narcolepsy-Cataplexy. B. Orexin/Hypocretin Deficiency in Human Narcolepsy and Other Conditions. Hypocretin Deficiency in Human Narcolepsy: Mutation Screening, Neuropathology, and CSF Hypocretin-1 Level. Hypocretin Status in Neurological Disorders in Relation to Excessive Sleepiness and Cataplexy. Hypocretin Measures in Psychiatric Disorders. Neuroendocrinology of Human Narcolepsy. Narcolepsy and Autoimmunity. C. Treatment/Pharmacology. Pharmacology of Orexin/Hypocretin Peptides and Small Molecules. Ectopic Overexpression of Orexin Peptides in Mouse Brains: Implications for Future Treatment of Narcolepsy-Cataplexy. Hypocretin/Orexin Replacement Therapy in Hypocretin/Orexin-Deficient Narcolepsy: An Overview.
 

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Contents

History and Overview of OrexinHypocretin Research
3
Orexin and Orexin Receptors
13
Orexin Projections and Localization of Orexin Receptors
21
Neuronal Responses to HypocretinOrexin
45
Afferent System of Orexin Neurons
61
Hypocretin Measurements in the CSF and Blood and Brain Tissue
73
Hypocretin ReceptorActivated G Proteins Revealed by ⁵SGTPγS Autoradiography
83
Orexin System and Feeding Behavior
99
HypocretinOrexin and Motor Function
209
Overview of Human Narcolepsy
221
Canine Models of Narcolepsy
233
Rodent Models of Human NarcolepsyCataplexy
255
Hypocretin Deficiency in Human Narcolepsy
269
Hypocretin Status in Neurological Disorders in Relation to Excessive Sleepiness and Cataplexy
287
Hypocretin Measures in Psychiatric Disorders
317
Neuroendocrinology of Human Narcolepsy
329

Orexins and the Autonomic Nervous System
107
Neuroendocrine Role of the Orexins Hypocretins
119
The OrexinHypocretin System and Stress and Emotion
131
Hypocretin as a Wakefulness Regulatory Peptide
143
HypocretinOrexin Tonus and Vigilance Control
155
Hypocretin System and Aminergic and Cholinergic Systems in the Control of Vigilance
175
Orexin and Hypothalamic Control of Sleep and Waking
189
Narcolepsy and Autoimmunity
341
Pharmacology of HypocretinOrexin Peptides and Small Molecules
349
Rescue of Narcoleptic Orexin NeuronAblated Mice by Ectopic Overexpression of Orexin Peptides
359
HypocretinOrexin Replacement Therapy in HypocretinOrexinDeficient Narcolepsy An Overview
367
INDEX
389
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