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 1.3 Keeping the transcriptional clockworks in tune 9 1.4 Building posttranslational mechanisms into the circadian pacemaker 13 1.5 Is the transcriptional clock paramount? 15 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 3.7 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 4.4 Reciprocity: sleep-wake feedback to the circadian clock 69 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 6.3 Circadian control of liver function 101 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 7.3 The FEO in peripheral tissues 109 7.
4 What should we eat? What types of food can stimulate the peripheral clock? 110 7.5 When should we eat? Application to human life science 112 7.6 Circadian rhythm and obesity and diabetes 113 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 a-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 10.3 Animal models 146 10.4 The circadian clock and micturition 147 10.
5 The clock in the bladder 148 10.6 Future directions 150 References 151 11 Disruption of Circadian Rhythms and Development of Type 2 Diabetes Mellitus: Contributions to Insulin Resistance and Beta?]cell Failure 155 Aleksey V. Matveyenko 11.1 Introduction 155 11.2 Mechanisms underlying pathophysiology of Type 2 diabetes mellitus: interaction between insulin resistance and beta-cell failure 156 11.3 Mechanisms underlying the association between circadian disruption and T2DM; potential role of obesity and insulin resistance 160 11.4 Mechanisms underlying the association between circadian disruption and T2DM; potential role of impaired beta-cell secretory function and mass 162 11.5 Conclusion 165 References 166 12 Circadian Clock Control of the Cell Cycle and Links to Cancer 169 T.
Katherine Tamai and David Whitmore 12.1 Introduction 169 12.2 Epidemiology 169 12.3 Does circadian clock disruption have any relevance in a clinical setting? 170 12.4 Circadian clock control of the cell cycle in healthy tissues 171 12.5 How might the cellular circadian clock regulate cell cycle timing? 173 12.6 Clock disruption and cancer 177 12.7 Does alteration in clock gene expression in human tumors correlate with the survival of patients? 178 12.
8 Circadian?]based chemotherapy (Chronotherapy): timing cancer treatment to improve survival 178 12.9 Conclusion 180 References 180 13 How Shift Work and a Destabilized Circadian System may Increase Risk for Development of Cancer and Type 2 Diabetes 183 An Pan, Elizabeth Devore, and Eva S. Schernhammer 13.1 Introduction 183 13.2 Shift work and cancer 184 13.3 Shift work and obesity, metabolic syndrome, and type 2 diabetes 194 13.4 Conclusions and perspective of future studies 205 References 205 14 Circadian Rhythms in Immune Function 211 Kandis Adams, Oscar Castanon- Cervantes, and Alec J. Davidson 14.
1 Introduction 211 14.2 Daily variations in health and disease 212 14.3 Early evidence of circadian regulation on immunity 212 14.4 Clinical relevance of circadian regulation of the immune system 213 14.5 The circadian system communicates time of day information to immune cells and tissues 214 14.6 Immune effector cells under circadian regulation 214 14.7 Circadian disruption role in immune pathology and disease 216 14.8 The effects of clock gene alterations on immune functions 217 14.
9 Conclusions 217 References 218 Part III Clocks in the Central Nervous System 221 15 Circadian Clock, Reward and Addictive Behavior 223 Urs Albrecht 15.1 Introduction 223 15.2 Evidence for a time of day basis of addictive behavior 223 15.3 Drugs, circadian clock genes and addictive behavior 224 15.4 Links between feeding, addictive behavior and the clock 228 15.5 Treatment of addiction changing the circadian clock 229 References 231 16 How a Disrupted Clock may Cause a Decline in Learning and Memory 235 Christopher S. Colwell 16.1 Introduction 235 16.
2 Molecular clockwork expressed in brain regions central to learning and memory including the hippocampus, amygdala, and cortex 236 16.3 The circadian clockwork regulates intracellular signaling pathways known to be important to learning and memory 237 16.4 The circadian system impacts electrical activity and synaptic plasticity 238 16.5 The circadian system regulates neuroendocrine secretions that are well known to alter learning and memory processes 240 16.6 Disruptions of the circadian timing system alter learned behavior 241 16.7 Conclusions 245 References 245 17 Circadian Rhythms in Mood Disorders 249 Colleen A. McClung 17.1 Introduction 249 17.
2 Categories of rhythm disruptions 251 17.3 Seasonal affective disorder 252 17.4 Treatments for mood disorders alter rhythms 253 17.5 Human genetic studies 257 17.6 Animal studies 257 17.7 SCN output?]rhythmic hormones and peptides 260 17.8 Regulation of mood?]related brain circuits by the SCN and circadian genes 262 17.9 Neuroinflammation 263 17.
10 Cell cycle regulation/neu.