Sleep and its Disorders: Translational Medicine

Description

The aim of this book is to provide health care professionals with an overview of the main aspects of recent advances in sleep medicine, with an emphasis on advancing basic science into clinical medicine. It is divided into three main parts. The first part is to cover the basic sleep mechanisms which includes genetics in sleep, and neural and humoral regulation of sleep and wakefulness. The second part focuses on the epidemiology of sleep, and the final part consists of the pathophysiological mechanisms of snoring and sleep apnea and other common sleep disorders as well as the consequences. The content of this book is written by experts and sleep specialists from all over the world and this book aims to optimize the health of individuals by “translating” bench side findings into clinical practice. Contents Part I: Basic Sleep Mechanisms Chapter 1: Evolving Approaches to Identifying Genetic Risk Variants for Sleep Disorders 1.1 UK Biobank 1.2 The Emerge Network/Health System Biobanks 1.3 Trans-omics for Precision Medicine (TOPMed) 1.4 Conclusion References Chapter 2: Neurobiology of Sleep-Wake Control 2.1 Introduction 2.2 Circadian Control of Sleep-Wake Behavior 2.3 Basic Rest-Activity Cycle (BRAC) and the Sleep-Wake Cycle 2.4 Neuroanatomy and Neurochemistry of Wakefulness and Sleep 2.4.1 Locations and Neurochemical Phenotypes of State-Dependent Neurons 2.4.2 Network Models of Generation of Sleep-Wake States 2.4.3 Atonia of REM Sleep 2.5 Mechanisms of Sleep-Wake Homeostasis 2.6 Conclusion References Additional Web Resources Offering a Complementary Overview of the Subject Chapter 3: Prostaglandins, Adenosine, and Histaminergic System in the Regulation of Sleep and Wakefulness 3.1 Introduction 3.2 Adenosine Is a Key Signaling Molecule for PGD2-Induced Sleep 3.3 Formation, Metabolism, and Transport of Adenosine in the CNS 3.4 Increase in the Extracellular Adenosine Level Promotes Sleep 3.5 Predominant Roles of A2AR in Sleep Regulation by Adenosine 3.6 A1R-Mediated Effects on Sleep-Wake Cycles Are Brain Region Dependent 3.7 Potential Application of Adenosine Receptor Agonists to Sleep Disorders 3.8 Histaminergic System Is Essential for Wakefulness 3.9 Conclusions References Chapter 4: Sleep and Neuronal Plasticity 4.1 Introduction 4.2 Sleep and Developmental Plasticity 4.2.1 Sleep and Ocular Dominance Plasticity 4.2.2 Sleep and Developmental LTP In Vitro 4.3 Sleep and Plasticity in the Adult Brain 4.3.1 LTP and LTD: In Vitro and In Vivo Studies in Adult Animals 4.3.2 Naturally Occurring Forms of Cortical and Hippocampal Plasticity 4.4 Models of Sleep-Dependent Plasticity 4.4.1 Replay-Reactivation of Waking Experience During Sleep 4.4.2 A Closer Look at Replay 4.4.3 The Synaptic Homeostasis Hypothesis 4.4.4 A Closer Look at SHY 4.5 Discussion References Part II: Insufficient Sleep and Its Consequences Chapter 5: Epidemiology of Insufficient Sleep 5.1 Defining Insufficient Sleep 5.2 Prevalence of Insufficient Sleep 5.2.1 Insufficient Sleep in the Population 5.2.2 Insufficient Sleep by Age 5.2.3 Insufficient Sleep by Sex 5.2.4 Insufficient Sleep by Race/Ethnicity 5.2.5 Insufficient Sleep by Socioeconomic Status 5.2.6 Insufficient Sleep by Geography 5.3 Insufficient Sleep and Epidemiology of Other Domains of Health 5.3.1 Insufficient Sleep and Mortality 5.3.2 Insufficient Sleep and Epidemiology of Obesity 5.3.3 Insufficient Sleep and Cardiovascular Epidemiology 5.3.4 Insufficient Sleep and Diabetes Epidemiology 5.3.5 Insufficient Sleep and Epidemiology of Daytime Dysfunction 5.4 Methodological Issues for Estimates of Insufficient Sleep in the Population References Chapter 6: Social Factors in Insufficient Sleep 6.1 Introduction 6.2 Age 6.3 Sex 6.4 Race/Ethnicity 6.5 Education 6.6 Family Structure 6.7 Family Income 6.8 Employment 6.9 Insufficient Sleep in Relation to Waking Activities 6.10 Conclusions References Chapter 7: Sleep Loss and the Unfolded Protein Response 7.1 Introduction 7.2 Unfolded Protein Response 7.2.1 The Adaptive Unfolded Protein Response 7.2.1.1 PERK Activation Leads to an Inhibition of Protein Translation and Activation of an Antioxidant Response 7.2.1.2 IRE1 Activation Leads to Upregulation of Chaperones, ER Expansion and Degradation of Transcripts, and Misfolded Protei... 7.2.1.3 Activated ATF6 Upregulates Chaperone Production 7.2.2 Prolonged ER Stress Leads to an Inflammatory Response and Apoptotic Signaling 7.3 UPR Pathways and Factors Induced by Sleep Loss in the Brain 7.3.1 Changes in ER Stress Response with Age 7.3.2 Chronic Sleep Loss 7.4 UPR Induction in Peripheral Tissues with Sleep Loss 7.5 Other Sleep Disturbances and the UPR 7.6 UPR Role in Sleep Regulation 7.7 Concluding Remarks: Implications for Human Diseases References Part III: Sleep Apnea Chapter 8: Biological and Genetic Mechanisms of Sleepiness in Obstructive Sleep Apnea and Cardiovascular Disease 8.1 Introduction 8.2 Genetic and Biological Markers of Oxidative Stress and Inflammation in OSA 8.2.1 Oxidative Stress in OSA 8.2.2 Select Candidate Gene Studies on Oxidative Stress and Sleepiness 8.2.3 Inflammation in OSA 8.2.4 Relevant Candidate Gene Studies on Inflammation and Sleepiness 8.2.5 Cardiovascular Sequelae of OSA and Sleepiness 8.3 Potential Therapies for Sleepiness in Sleep Apnea 8.4 Summary and Future Research Implications References Chapter 9: Diaphragm EMG Recording and Its Application in Sleep Medicine 9.1 Recording of Diaphragm EMG 9.2 Assessment of Neural Respiratory Drive with Diaphragm EMG 9.3 Neural Drive During Apneic Events in Patients with OSA 9.4 The Mechanism of Arousal in Patients with OSA 9.5 Distinguishing Central from Obstructive Sleep Apnea Events 9.6 Neural Respiratory Drive in Patients with COPD Alone During Sleep 9.7 Neural Respiratory Drive in Patients with Both COPD and OSA During Sleep 9.8 Conclusion References Chapter 10: Chronic Intermittent Hypoxia in Patients with OSA 10.1 Introduction 10.2 CIH and Cardiovascular Diseases 10.2.1 Clinical Evidence 10.2.1.1 Hypertension 10.2.1.2 Pulmonary Hypertension 10.2.1.3 Cardiac Arrhythmias 10.2.1.4 Coronary Artery Disease 10.2.1.5 Heart Failure 10.2.1.6 Stroke 10.2.2 Mechanisms 10.2.2.1 Dysregulation of Autonomic Nervous System 10.2.2.2 Oxidative Stress and Inflammation 10.2.2.3 Endothelial Dysfunction 10.3 CIH and Metabolic Dysfunction 10.3.1 CIH and Impaired Glucose Metabolism: Clinical Evidence 10.3.2 CIH and Impaired Glucose Metabolism: Mechanisms 10.3.2.1 CIH and Insulin Resistance 10.3.2.2 CIH and β-Cell Dysfunction 10.3.3 CIH and Impaired Lipid Metabolism: Clinical Evidence 10.3.4 CIH and Impaired Lipid Metabolism: Mechanisms 10.4 CIH and Neurocognitive Dysfunction 10.4.1 Clinical Evidence 10.4.2 Mechanisms 10.5 CIH and Tumor 10.5.1 Clinical Evidence 10.5.2 Mechanisms References Chapter 11: Neural Injury in Models of Intermittent Hypoxia 11.1 Intermittent Hypoxia from the Clinical Perspective 11.2 Historical Perspective of IH Animal Studies and Various Patterns of IH Examined 11.2.1 Chronic Sustained Intermittent Hypoxia 11.2.2 Early Studies of IH Studies Specifically Modeling OSA 11.2.3 Chronic Versus Sustained IH Effects on the Brain 11.3 Beneficial Effects of Acute Intermittent Hypoxia on Phrenic Nerve Function 11.4 The ``More Is Not Better´´ Side of Intermittent Hypoxia 11.4.1 Effects of Chronic Intermittent Hypoxia on Carotid Body Activation 11.4.1.1 Oxygen Sensing at the Carotid Body Across IH 11.4.1.2 Chronic IH Activation of Sympathetic Activity 11.4.2 Chronic Intermittent Hypoxia Impact on Hippocampal Neurons and Function 11.5 Molecular Mechanisms by Which LTIH Impairs Wakefulness 11.6 LTIH Injury to Upper Airway Motoneurons 11.7 LTIH Effect on Glial Cells 11.8 Concluding Remarks References Part IV: Narcolepsy Chapter 12: Narcolepsy and Orexin/Hypocretin 12.1 Biology of Orexin System 12.1.1 Orexin and Orexin Receptors 12.1.2 Orexin-Producing Neuron and Its Neuronal Innervation 12.1.3 Neurochemical Interactions of the Orexin 12.1.4 Physiological Functions of Orexin 12.2 Clinical Aspects of Narcolepsy 12.2.1 Epidemiology 12.2.2 Clinical Manifestation of Narcolepsy 12.2.2.1 Excessive Daytime Sleepiness and Related Symptoms 12.2.2.2 Cataplexy 12.2.2.3 Sleep Paralysis 12.2.2.4 Hypnagogic and Hypnopompic Hallucinations 12.2.2.5 Other Important Symptoms 12.2.3 Diagnosis 12.2.3.1 Polysomnography, Symptoms, and Sleep Evaluations 12.2.3.2 Biological Markers 12.2.3.3 Diagnosis of Narcolepsy 12.2.3.4 Differential Diagnosis 12.3 Narcolepsy and Orexin: From Basic Science Research into Clinical Practice 12.3.1 Deficient Orexin in Narcolepsy and Diagnostic Value of CSF Orexin Measurement 12.3.1.1 Dog and Rodent Models of Narcolepsy 12.3.1.2 Orexin Deficiency in Human Narcolepsy 12.3.1.3 Similar Phenotype of Narcolepsy-Cataplexy in Humans and Mice 12.3.1.4 Measurement of CSF Orexin in the Diagnosis of Narcolepsy 12.3.2 HLA Genetic Marker in Narcolepsy 12.3.3 Narcolepsy and Sleep Apnea 12.3.3.1 Respiratory Regulation and Orexin/Hypocretin in Narcoleptic Animal Models 12.3.3.2 Respiratory Regulation and Orexin/Hypocretin in Human Narcolepsy 12.3.4 Treatment of Narcolepsy 12.4 Conclusion References Part V: Circadian Rhythm Disorders Chapter 13: Circadian Rhythm Sleep-Wake Disorders: Mechanisms and Treatment 13.1 Introduction 13.2 Delayed Sleep-Wake Phase Disorder 13.3 Advanced Sleep-Wake Phase Disorder 13.4 Irregular Sleep-Wake Rhythm Disorder 13.5 Non-24-Hour Sleep-Wake Rhythm Disorder 13.6 Shift Work Disorder 13.7 Jet Lag Disorder 13.8 Conclusions References