Circadian Medicine

Christopher S. Colwell is a neuroscientist and Professor in the Department of Psychiatriary and Biobehavioral Sciences at the University of California, Los Angeles.

• List of Contributors xiiiPreface xviiPart I Fundamental Concepts 11 Cytosolic and TranscriptionalCycles Underlying Circadian Oscillations 3Michael H. Hastings and John S. O’Neill1.1 Introduction 31.2 Assembling the transcriptional feedback loop 51.3 Keeping the transcriptional clockworks in tune 91.4 Building posttranslational mechanisms into the circadian pacemaker 131.5 Is the transcriptional clock paramount? 151.6 Conclusion: cytoscillators, clocks and therapies 18References 182 Molecular Determinants of Human Circadian Clocks 25Steven A. Brown2.1 Molecular elements of human clocks: a brief review 252.2 Peripheral and central clocks 262.3 Signaling to peripheral circadian clocks 282.4 Human peripheral and central clocks 292.5 Human genetics 292.6 Technologies for measurement of human circadian clocks 302.7 Cellular methods 302.8 Omics]based methods to analyze human clocks 322.9 Summary and outlook 33References 333 The Suprachiasmatic Nucleus (SCN): Critical Points 37Christopher S. Colwell, Paul Witkovsky, and Rae Silver3.1 SCN is site of master circadian pacemaker in mammals 373.2 SCN receives photic information through a specialized light detection pathway 393.3 SCN neurons are endogenous single cell oscillators that generate rhythms in neural activity 403.4 The SCN has circuit level organization that is just beginning to be unraveled 423.5 Coupling with the SCN circuit is mediated by a set of peptides with VIP on top of the hierarchy 443.6 SCN outputs 443.7 SCN in aging and disease 50References 514 Sleep and Circadian Rhythms: Reciprocal Partners in the Regulation of Physiology and Behavior 57Ralph Mistlberger4.1 Introduction 574.2 What is sleep 594.3 Circadian regulation of sleep 604.4 Reciprocity: sleep–wake feedback to the circadian clock 694.5 Conclusions: Circadian clocks and sleep are intertwined processes 73References 735 Circadian Regulation of Arousal and its Role in Fatigue 81David R. Bonsall and Mary E. Harrington5.1 Defining arousal 815.2 Brain structures important for arousal 835.3 Neurochemicals signaling the states of arousal 845.4 Circadian regulation of the arousal system 865.5 Influence of input pathways on circadian regulation of arousal 885.6 Sustained states of fatigue: a disorder of the arousal network? 885.7 Conclusions 90References 91Part II Circadian Regulation of Major Physiological Systems 956 Physiology of the Adrenal and Liver Circadian Clocks 97Alexei Leliavski and Henrik Oster6.1 Introduction 976.2 Circadian control of adrenal function 986.3 Circadian control of liver function 1016.4 Conclusion 105References 1057 Nutrition and Diet as Potent Regulators of the Liver Clock 107Yu Tahara and Shigenobu Shibata7.1 Introduction 1077.2 Food is a “zeitgeber”: The FEO in the brain 1077.3 The FEO in peripheral tissues 1097.4 What should we eat? What types of food can stimulate the peripheral clock? 1107.5 When should we eat? Application to human life science 1127.6 Circadian rhythm and obesity and diabetes 113References 1168 The Cardiovascular Clock 119R. Daniel Rudic8.1 Introduction 1198.2 The vascular clock 1198.3 Circadian clock regulation of the endothelial cell layer of blood vessels 1208.4 The circadian clock in vascular disease 1218.5 The circadian clock and vascular cell signaling 1228.6 The circadian rhythm in blood pressure, nighttime hypertension, and cardiovascular disease in humans 1238.7 Diabetes, obesity, and blood pressure 1258.8 AT influences the circadian rhythm in experimental hypertension 1268.9 The circadian clock and fluid balance 1278.10 The circadian clock and peripheral vascular resistance 1278.11 Conclusion 130References 1309 Hypertension Caused by Disruption of the Circadian System: Blood Pressure Regulation at Multiple Levels 135Hitoshi Okamura, Miho Yasuda, Jean]Michel Fustin, and Masao Doi9.1 Introduction 1359.2 Effects of deleting Cry genes 1359.3 Reduced a-adrenoceptor responsiveness in peripheral vessels and primary aldosteronism of Cry-null mice 1389.4 Rapid blood pressure control system: enhanced baroreflex in Cry-null mice 1399.5 Conclusion 141References 14110 Chronobiology of Micturition 143Akihiro Kanematsu and Hiromitsu Negoro10.1 Introduction 14310.2 Human studies 14410.3 Animal models 14610.4 The circadian clock and micturition 14710.5 The clock in the bladder 14810.6 Future directions 150References 15111 Disruption of Circadian Rhythms and Development of Type 2 Diabetes Mellitus: Contributions to Insulin Resistance and Beta]cell Failure 155Aleksey V. Matveyenko11.1 Introduction 15511.2 Mechanisms underlying pathophysiology of Type 2 diabetes mellitus: interaction between insulin resistance and beta-cell failure 15611.3 Mechanisms underlying the association between circadian disruption and T2DM; potential role of obesity and insulin resistance 16011.4 Mechanisms underlying the association between circadian disruption and T2DM; potential role of impaired beta-cell secretory function and mass 16211.5 Conclusion 165References 16612 Circadian Clock Control of the Cell Cycle and Links to Cancer 169T. Katherine Tamai and David Whitmore12.1 Introduction 16912.2 Epidemiology 16912.3 Does circadian clock disruption have any relevance in a clinical setting? 17012.4 Circadian clock control of the cell cycle in healthy tissues 17112.5 How might the cellular circadian clock regulate cell cycle timing? 17312.6 Clock disruption and cancer 17712.7 Does alteration in clock gene expression in human tumors correlate with the survival of patients? 17812.8 Circadian]based chemotherapy (Chronotherapy): timing cancer treatment to improve survival 17812.9 Conclusion 180References 18013 How Shift Work and a Destabilized Circadian System may Increase Risk for Development of Cancer and Type 2 Diabetes 183An Pan, Elizabeth Devore, and Eva S. Schernhammer13.1 Introduction 18313.2 Shift work and cancer 18413.3 Shift work and obesity, metabolic syndrome, and type 2 diabetes 19413.4 Conclusions and perspective of future studies 205References 20514 Circadian Rhythms in Immune Function 211Kandis Adams, Oscar Castanon-Cervantes, and Alec J. Davidson14.1 Introduction 21114.2 Daily variations in health and disease 21214.3 Early evidence of circadian regulation on immunity 21214.4 Clinical relevance of circadian regulation of the immune system 21314.5 The circadian system communicates time of day information to immune cells and tissues 21414.6 Immune effector cells under circadian regulation 21414.7 Circadian disruption role in immune pathology and disease 21614.8 The effects of clock gene alterations on immune functions 21714.9 Conclusions 217References 218Part III Clocks in the Central Nervous System 22115 Circadian Clock, Reward and Addictive Behavior 223Urs Albrecht15.1 Introduction 22315.2 Evidence for a time of day basis of addictive behavior 22315.3 Drugs, circadian clock genes and addictive behavior 22415.4 Links between feeding, addictive behavior and the clock 22815.5 Treatment of addiction changing the circadian clock 229References 23116 How a Disrupted Clock may Cause a Decline in Learning and Memory 235Christopher S. Colwell16.1 Introduction 23516.2 Molecular clockwork expressed in brain regions central to learning and memory including the hippocampus, amygdala, and cortex 23616.3 The circadian clockwork regulates intracellular signaling pathways known to be important to learning and memory 23716.4 The circadian system impacts electrical activity and synaptic plasticity 23816.5 The circadian system regulates neuroendocrine secretions that are well known to alter learning and memory processes 24016.6 Disruptions of the circadian timing system alter learned behavior 24116.7 Conclusions 245References 24517 Circadian Rhythms in Mood Disorders 249Colleen A. McClung17.1 Introduction 24917.2 Categories of rhythm disruptions 25117.3 Seasonal affective disorder 25217.4 Treatments for mood disorders alter rhythms 25317.5 Human genetic studies 25717.6 Animal studies 25717.7 SCN output]rhythmic hormones and peptides 26017.8 Regulation of mood]related brain circuits by the SCN and circadian genes 26217.9 Neuroinflammation 26317.10 Cell cycle regulation/neurogenesis 26417.11 Conclusions 265References 26518 Sleep and Circadian Rhythm Disruption in Psychosis 271Stuart N. Peirson and Russell G. Foster18.1 Introduction 27118.2 Psychosis 27318.3 Sleep and circadian rhythm disruption in psychosis 27518.4 Possible mechanisms underlying SCRD in psychosis 27718.5 Conclusions 280References 28119 Alzheimer’s Disease and the Mistiming of Behavior 283Roxanne Sterniczuk and Michael Antle19.1 Introduction 28319.2 Behavioral changes 28319.3 Physiological changes 28519.4 Neurological changes 28619.5 Modeling AD 28919.6 Chronobiological treatment of AD symptomology 29019.7 Conclusion 292References 29320 Circadian Dysfunction in Parkinson’s Disease 295Christopher S. Colwell20.1 Introduction 29520.2 Dysfunction in the circadian system may contribute to the nonmotor symptoms of PD 29620.3 Dopaminergic treatments for the motor symptoms of PD may contribute to circadian disruption 29720.4 PD models show sleep and possible circadian disruption 29820.5 Possible underlying mechanisms 30020.6 Conclusion 301References 30221 Circadian Dysfunction in Huntington’s Disease 305A. Jennifer Morton21.1 Introduction 30521.2 Mechanisms underlying sleep and circadian rhythm generation 30521.3 Circadian disruption in HD 30621.4 Circadian disruption in animal models of HD 30621.5 Circadian disruption of peripheral clocks and metabolism in HD 31121.6 Pharmacological manipulation of circadian disruption in HD mice 31121.7 Environmental modulation of circadian disruption in HD mice 31121.8 Clinical changes in sleep in HD 31221.9 Disturbance in sleep architecture in HD 31221.10 Pathology underlying changes in sleep and circadian activity in HD 31321.11 The orexin system in HD 31321.12 The role of non]SCN oscillators in HD 31421.13 Consequences of sleep–wake disturbance in HD 31421.14 Cognitive dysfunction and mood disturbance in HD 31521.15 Management of circadian disturbance in HD 31521.16 Conclusions 317References 31822 The Aging Clock 321Stephan Michel, Gene D. Block, and Johanna H. Meijer22.1 Introduction 32122.2 The effects of aging on rhythmic behaviors 32122.3 The effects of aging on components of the circadian system 32322.4 Molecular rhythms in steady state 32822.5 The effects of aging on the resetting behavior of central and peripheral oscillators 32922.6 The effects of the circadian system on aging and age]related disease: Circadian misalignment andlongevity 33022.7 Therapeutic possibilities for agerelated circadian disorders 33122.8 Conclusions 332References 33223 Can we Fix a Broken Clock? 337Analyne M. Schroeder and Christopher S. Colwell23.1 Introduction 33723.2 Light therapy 33923.3 Scheduled meals 34023.4 Scheduled exercise 34123.5 Scheduled sleep 34323.6 Pharmacological targeting of the circadian system 34323.7 Conclusions 345References 346Index 351