Circadian rhythms, the biological oscillations based around our 24-hour clock, have a profound effect on human physiology and healthy cellular function. Circadian Rhythms: Health and Disease is a wide-ranging foundational text that provides students and researchers with valuable information on the molecular and genetic underpinnings of circadian rhythms and looks at the impacts of disruption in our biological clocks in health and disease.
Circadian Rhythms opens with chapters that lay the fundamental groundwork on circadian rhythm biology. Section II looks at the impact of circadian rhythms on major organ systems. Section III then turns its focus to the central nervous system. The book then closes with a look at the role of biological rhythms in aging and neurodegeneration.
Written in an accessible and informative style, Circadian Rhythms: Health and Disease,will be an invaluable resource and entry point into this fascinating interdisciplinary field that brings together aspects of neuroscience, cell and molecular biology, and physiology.
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List of Contributors xiii Preface xvii Part I Fundamental Concepts 1 1 Cytosolic and Transcriptional Cycles Underlying Circadian Oscillations 3 Michael H. Hastings and John S. O Neill 1.1 Introduction 3 1.2 Assembling the transcriptional feedback loop 5 1.2.1 Discovering clock genes and their actions in lower species 5 1.2.2 Discovering clock genes and their actions in mammals 6 1.2.3 Imaging the transcriptional clock in real time: a multitude of cellular oscillators appears 6 1.2.4 Elaborating the core transcriptional clockwork 8 1.3 Keeping the transcriptional clockworks in tune 9 1.3.1 Entrainment of the SCN transcriptional clockwork 9 1.3.2 Entrainment of transcriptional clocks in peripheral tissues 10 1.3.3 Local tissue clocks direct local transcriptional and posttranscriptional programs 11 1.4 Building posttranslational mechanisms into the circadian pacemaker 13 1.4.1 Posttranslational control of the clock: localization and stability of clock proteins 13 1.4.2 Metabolic regulation of the transcriptional clockwork 13 1.4.3 Cause versus effect in circadian transcriptional regulation 14 1.5 Is the transcriptional clock paramount? 15 1.5.1 Cytosolic rhythms and the SCN pacemaker 15 1.5.2 Totally transcription ]free pacemaking 16 1.5.3 A general model for mammalian cellular circadian timekeeping 17 1.6 Conclusion: cytoscillators, clocks and therapies 18 References 18 2 Molecular Determinants of Human Circadian Clocks 25 Steven A. Brown 2.1 Molecular elements of human clocks: a brief review 25 2.2 Peripheral and central clocks 26 2.3 Signaling to peripheral circadian clocks 28 2.4 Human peripheral and central clocks 29 2.5 Human genetics 29 2.6 Technologies for measurement of human circadian clocks 30 2.7 Cellular methods 30 2.8 Omics ]based methods to analyze human clocks 32 2.9 Summary and outlook 33 References 33 3 The Suprachiasmatic Nucleus (SCN): Critical Points 37 Christopher S. Colwell, Paul Witkovsky, and Rae Silver 3.1 SCN is site of master circadian pacemaker in mammals 37 3.2 SCN receives photic information through a specialized light detection pathway 39 3.3 SCN neurons are endogenous single cell oscillators that generate rhythms in neural activity 40 3.4 The SCN has circuit level organization that is just beginning to be unraveled 42 3.5 Coupling with the SCN circuit is mediated by a set of peptides with VIP on top of the hierarchy 44 3.6 SCN outputs 44 3.6.1 SCN neurons are directly neurosecretory cells 45 3.6.2 Body temperature rhythms as an output 47 3.6.3 SCN regulates the autonomic nervous system 47 3.6.4 Melatonin is a key hormone under circadian regulation 47 3.6.5 HPA axis is another important endocrine network regulated by the circadian system 49 3.6.6 The SCN regulates the arousal of the central nervous system 49 3.6.7 The SCN circuit controls the temporal patterning behaviors (activity, sleep, feeding) with widespread implications for our bodily function 50 3.7 SCN in aging and disease 50 References 51 4 Sleep and Circadian Rhythms: Reciprocal Partners in the Regulation of Physiology and Behavior 57 Ralph Mistlberger 4.1 Introduction 57 4.2 What is sleep 59 4.3 Circadian regulation of sleep 60 4.3.1 Behavioral studies: human sleep 60 4.3.2 Behavioral studies: rodent models 63 4.3.3 Neural mechanisms 64 4.3.4 Molecular mechanisms, local oscillators and local sleep 66 4.4 Reciprocity: sleep wake feedback to the circadian clock 69 4.4.1 Feedback from waking states 69 4.4.2 Feedback from sleep states 71 4.5 Conclusions: Circadian clocks and sleep are intertwined processes 73 References 73 5 Circadian Regulation of Arousal and its Role in Fatigue 81 David R. Bonsall and Mary E. Harrington 5.1 Defining arousal 81 5.2 Brain structures important for arousal 83 5.3 Neurochemicals signaling the states of arousal 84 5.4 Circadian regulation of the arousal system 86 5.5 Influence of input pathways on circadian regulation of arousal 88 5.6 Sustained states of fatigue: a disorder of the arousal network? 88 5.7 Conclusions 90 References 91 Part II Circadian Regulation of Major Physiological Systems 95 6 Physiology of the Adrenal and Liver Circadian Clocks 97 Alexei Leliavski and Henrik Oster, 6.1 Introduction 97 6.2 Circadian control of adrenal function 98 6.2.1 Glucocorticoids (GCs) 99 6.2.2 Mineralocorticoids (MCs) 99 6.2.3 Catecholamines (CAs) 99 6.2.4 Adrenal clocks 100 6.2.5 Local control of MC rhythms 100 6.2.6 Local control of GC rhythms 101 6.3 Circadian control of liver function 101 6.3.1 Glucose metabolism 102 6.3.2 Lipid metabolism 103 6.3.3 Detoxification 103 6.3.4 Hepatocyte clocks 104 6.3.5 Local control of energy metabolism 104 6.3.6 Local control of biotransformation 104 6.4 Conclusion 105 References 105 7 Nutrition and Diet as Potent Regulators of the Liver Clock 107 Yu Tahara and Shigenobu Shibata 7.1 Introduction 107 7.2 Food is a zeitgeber : The FEO in the brain 107 7.2.1 Food entrainment and food anticipatory activity 107 7.2.2 Role of the SCN on the FEO 108 7.2.3 FEO formation and characteristics in the brain 108 7.3 The FEO in peripheral tissues 109 7.3.1 Discovery of the FEO in peripheral tissues 109 7.3.2 Effect of meal frequency and pattern on the FEO 110 7.3.3 Role of clock genes in FAA and FEO in the brain and FEO in peripheral tissues 110 7.4 What should we eat? What types of food can stimulate the peripheral clock? 110 7.4.1 Role of nutrients in the FEO 110 7.4.2 Foods beyond nutrients 111 7.4.3 Signal transduction in peripheral FEO 111 7.5 When should we eat? Application to human life science 112 7.6 Circadian rhythm and obesity and diabetes 113 7.6.1 Feeding frequency and patterns affect obesity and diabetes 113 7.6.2 Effect of rotation work and shift work on obesity, diabetes, and cancer 114 7.6.3 Effect of calorie restriction on circadian rhythm and life span 114 7.6.4 Role of circadian rhythm in pharmacological and nutritional actions 115 References 116 8 The Cardiovascular Clock 119 R. Daniel Rudic 8.1 Introduction 119 8.2 The vascular clock 119 8.3 Circadian clock regulation of the endothelial cell layer of blood vessels 120 8.4 The circadian clock in vascular disease 121 8.5 The circadian clock and vascular cell signaling 122 8.6 The circadian rhythm in blood pressure, nighttime hypertension, and cardiovascular disease in humans 123 8.7 Diabetes, obesity, and blood pressure 125 8.8 AT influences the circadian rhythm in experimental hypertension 126 8.9 The circadian clock and fluid balance 127 8.10 The circadian clock and peripheral vascular resistance 127 8.11 Conclusion 130 References 130 9 Hypertension Caused by Disruption of the Circadian System: Blood Pressure Regulation at Multiple Levels 135 Hitoshi Okamura, Miho Yasuda, Jean ]Michel Fustin, and Masao Doi 9.1 Introduction 135 9.2 Effects of deleting Cry genes 135 9.3 Reduced ]adrenoceptor responsiveness in peripheral vessels and primary aldosteronism of Cry ]null mice 138 9.4 Rapid blood pressure control system: enhanced baroreflex in Cry ]null mice 139 9.5 Conclusion 141 References 141 10 Chronobiology of Micturition 143 Akihiro Kanematsu and Hiromitsu Negoro 10.1 Introduction 143 10.2 Human studies 144 10.2.1 Children and nocturnal enuresis 144 10.2.2 Aging and nocturia 144 10.2.3 Nocturnal polyuria 144 10.2.4 Daily change in bladder capacity 145 10.2.5 Central control of the kidneys and the bladder 145 10.3 Animal models 146 10.3.1 Rats 146 10.3.2 Mice 146 10.4 The circadian clock and micturition 147 10.5 The clock in the bladder 148 10.5.1 The bladder has rhythm: demonstration of the circadian clock in the bladder 148 10.5.2 Connexin43 (Cx43) is a clockcontrolled gene in the bladder 149 10.6 Future directions 150 10.6.1 Basic research 150 10.6.2 Clinical research 151 References 151 11 Disruption of Circadian Rhythms and Development of Type 2 Diabetes Mellitus: Contributions to Insulin Resistance an
