Sleep and its Disorders: Translational Medicine

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