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Stress: Neuroendocrinology and Neurobiology - 1st Edition - ISBN: 9780128021750, 9780128024232

Stress: Neuroendocrinology and Neurobiology

1st Edition

Handbook of Stress Series, Volume 2

Editor: George Fink
Hardcover ISBN: 9780128021750
eBook ISBN: 9780128024232
Imprint: Academic Press
Published Date: 15th December 2016
Page Count: 460
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Stress: Neuroendocrinology and Neurobiology: Handbook of Stress Series, Volume 2, focuses on neuroendocrinology, the discipline that deals with the way that the brain controls hormonal secretion, and in turn, the way that hormones control the brain. There have been significant advances in our understanding of neuroendocrine molecular and epigenetic mechanisms, especially in the way in which stress-induced hormonal and neurochemical changes affect brain plasticity, neuronal connectivity, and synaptic function.

The book features the topic of epigenetics, and how it enables stress and other external factors to affect genetic transmission and expression without changes in DNA sequence. Integrated closely with new behavioral findings and relevance to human disorders, the concepts and data in this volume offer the reader cutting-edge information on the neuroendocrinology of stress.

Volume 2 is of prime interest to neuroscientists, clinicians, researchers, academics, and graduate students in neuroendocrinology, neuroscience, biomedicine, endocrinology, psychology, psychiatry, and in some areas of the social sciences, including stress and its management in the workplace.

Key Features

  • Includes chapters that offer impressive scope with topics addressing the neuroendocrinology and endocrinology of stress
  • Presents articles carefully selected by eminent stress researchers and prepared by contributors that represent outstanding scholarship in the field
  • Richly illustrated, with explanatory figures and tables


Neuroscientists, neuroendocrinologists, neurologists, neuropharmacologists, and researchers, graduate students and post-doctoral fellows in neuroscience, psychology and the biomedical sciences

Table of Contents

Part I. Neuroendocrine Control of the Stress Response

  • Chapter 1. Stress Neuroendocrinology: Highlights and Controversies
    • Introduction
    • Neuroendocrine and Autonomic Nervous Control of Stress Response
    • Thrifty Phenotype Hypothesis: Variance Between Studies and Broadened to Include Maternal Obesity and Diabetes
    • Genetic Susceptibility to Stress: Gene×Environment Interaction
    • Posttraumatic Stress Disorder: Autonomic Nervous System Apparently Dominant
    • Human Hippocampus and Major Depressive Disorder: Does Hippocampal Size Matter?
    • Gastroduodenal (Peptic) Ulcers: Stress–Helicobacter pylori Interactions
    • General Conclusions and Observations
  • Chapter 2. Limbic Forebrain Modulation of Neuroendocrine Responses to Emotional Stress
    • Introduction
    • Kinds of Stress and Their Underpinnings
    • Limbic Modulation of the HPA Axis
    • Excitatory Modulation: Amygdala
    • Inhibitory Modulation: Hippocampal Formation and Medial Prefrontal Cortex
    • Mechanisms of HPA Modulation Following Repeated Stress Exposure
    • Future Perspective
  • Chapter 3. Adrenergic Neurons in the CNS
    • Localization
    • Projections
    • Neurochemistry
    • Functions
    • Activating Stimuli
    • Conclusion
  • Chapter 4. Noradrenergic Control of Arousal and Stress
    • Arousal-Promoting Actions of Central Norepinephrine
    • Broad Contributions of NE to Behavioral Responding in Stress
    • Clinical Implications
    • Summary
  • Chapter 5. Evolution and Phylogeny of the Corticotropin-Releasing Factor Family of Peptides
    • Introduction
    • Evolution of the CRF Family in Chordates and Role With the HPA Axis
    • Prechordate Evolution of the CRF Family
  • Chapter 6. Corticotropin-Releasing Factor and Urocortin Receptors
    • Introduction
    • Corticotropin-Releasing Factor and Urocortin Receptor Family
    • Pharmacology of CRF1 and CRF2 Receptors
    • Small Molecule Nonpeptide CRF1 Receptor Antagonists
    • Clinical Experience and Relevance
    • Summary and Conclusions
  • Chapter 7. Tracking the Coupling of External Signals to Intracellular Programs Controlling Peptide Synthesis and Release in Hypothalamic Neuroendocrine Neurons
    • Introduction
    • The PVH and CRH Neuroendocrine Neurons
    • Hindbrain Catecholamine Inputs to the CRH Neuroendocrine System
    • In Vivo Interrogation of Catecholamine-CRH Neuron Coupling
    • MAP Kinase as a Rapidly Activated Intracellular Effector in CRH Neuroendocrine Neurons In Vivo
    • Catecholamines Are Sufficient to Recapitulate Effects of Glycemic Challenges on CRH Neurons
    • Catecholaminergic Projections From Hindbrain Are Necessary for CRH Responses to Glycemic Challenges
    • A Model for CRH Neuroendocrine Neuron Signal-Effector Coupling
    • Extending the Study to a Larger Network: Focus on the Arcuate Hypothalamic Nucleus
    • Future Directions
  • Chapter 8. Neural Circuitry of Stress, Fear, and Anxiety: Focus on Extended Amygdala Corticotropin-Releasing Factor Systems
    • Introduction: Corticotropin-Releasing Factor
    • Organization of the EA CRF System
    • Extending the Amygdala: CRF Systems and the Neural Circuitry of Stress, Fear, and Anxiety
    • Reciprocal Connections Between EA CRF and Serotonergic Systems Modulate Anxiety
    • EA CRF Projections to the Locus Coeruleus Facilitate Stress-Induced Arousal and Anxiety States
    • EA CRF System at the Interface of Stress and Motivation/Reward
    • EA CRF Neurons Receives Peptidergic Input From the Parabrachial Nucleus
    • CRF Interaction With the Brain Renin-Angiotensin System
    • EA CRF Neurons and Central Autonomic Control
    • EA CRF Neurons Modulate Hypothalamic–Pituitary–Adrenal Axis Activity
    • Conclusions and Future Directions
  • Chapter 9. Vasopressin as a Stress Hormone
    • Introduction
    • Vasopressin and Its Distribution in the Brain and the Pituitary Gland
    • Molecular and Cellular Physiology of Vasopressin With Special Reference to Anterior Pituitary Corticotrope Cells
    • Functions of Vasopressin
    • Summary
  • Chapter 10. Adrenocorticotropic Hormone
    • Introduction
    • Adrenocorticotropic Hormone and Proopiomelanocortin
    • Adrenocorticotropic Hormone Production and Release From Pituitary Corticotropes
    • Control of Secretion
    • Negative Feedback Mechanisms
    • Clinical Perspectives
    • Other Effects of Adrenocorticotropic Hormone
    • Therapeutic Uses
    • Conclusion
  • Chapter 11. The Role of MicroRNAs in Stress-Induced Psychopathologies
    • Introduction
    • microRNAs
    • The Role of miRNAs in Fear Conditioning
    • Transgenerational Effects of Stress Mediated by Sperm miRNAs
    • Circulating miRNAs as Biomarkers for Stress-Related Psychopathologies
    • Open Questions and Future Directions
    • Concluding Remarks
  • Chapter 12. Stress Reactions Orchestrate Parasympathetic Functioning and Inflammation Under Diverse Cholinergic Manipulations
    • Introduction
    • Body to Brain Signaling of Stress and Inflammation
    • MicroRNAs-Driven Cholinergic Modulation of Inflammation
    • New Technologies: RNA-Sequence Profiling and Chemically Protected Antisense Oligonucleotides
    • Summary and Future Prospects
  • Chapter 13. Early Life Stress- and Sex-Dependent Effects on Hippocampal Neurogenesis
    • Stress, Time Domains, and Mediators of the Stress Response
    • Adult Neurogenesis
    • Stress and Adult Hippocampal Neurogenesis
    • Long-Lasting Effects of Early, Perinatal Stress Exposure; Sex Differences
    • Concluding Remarks
  • Chapter 14. Stress, Alcohol and Epigenetic Transmission
    • The Stress Response System
    • Alcohol (Ethanol) and the Stress Response
    • Alcohol, Epigenetic and Stress Response
    • Transgenerational Effect of Alcohol Epigenetic Marks
    • Conclusion
  • Chapter 15. Stress, Panic, and Central Serotonergic Inhibition
    • Introduction
    • Neurobiology of Panic Disorder and Panic Attacks
    • Anatomical and Functional Heterogeneity of Serotonergic Systems
    • Dorsal Raphe Nucleus (DR) Innervation of Escape- or Panic-Related Structures
    • Conclusion
  • Chapter 16. Neuroendocrinology of Posttraumatic Stress Disorder: Focus on the HPA Axis
    • Introduction: Adapative and Maladaptive Responses of the Hypothalamic–Pituitary–Adrenal Axis
    • Negative Feedback/Glucocorticoid Receptor
    • Perturbations of the HPA Axis as a Vulnerability Factor in the Development of PTSD
    • Conclusions and Future Directions
  • Chapter 17. Stress and Major Depression: Neuroendocrine and Biopsychosocial Mechanisms
    • Introduction
    • Neuroendocrine Mechanisms of Normal Stress Response
    • Neuroendocrine Abnormalities in Chronic Stress and Depression
    • Mechanisms of Antidepressant Action
    • Psychosocial Stress and Depression: A Biopsychosocial Perspective
    • Conclusion
  • Chapter 18. Telomeres and Early Life Stress
    • Introduction
    • An Introduction to Telomere Biology
    • Factors Impacting Telomere Length
    • Telomeres in Human Health and Disease
    • Early Life Stress and Telomeres
    • Potential Mechanisms Underlying the Association Between Early Life Stress and Telomere Length
    • Methodological Issues in Studies of Telomeres and Early Life Stress
    • Effects of Telomeres on Cellular Biology
    • Future Directions

Part II. Endocrine Systems and Mechanisms in Stress Control

  • Chapter 19. Stress, Glucocorticoids, and Brain Development in Rodent Models
    • Introduction
    • Stressors, Glucocorticoids, and the Hypothalamic–Pituitary–Adrenal Axis
    • Fetal Period
    • Neonatal Period
    • Adolescence
    • Conclusions and New Directions
  • Chapter 20. Aging and Adrenocortical Factors
    • Introduction
    • The Hypothalamic–Pituitary–Adrenal Axis
    • The Hypothalamic–Pituitary–Adrenal Axis and Normal Aging
    • Theories Relating to Age-Related Change
    • Summary and Conclusion
  • Chapter 21. Aldosterone and Mineralocorticoid Receptors
    • Background
    • Aldosterone Secretion: Adrenal and Extraadrenal
    • Regulation of Aldosterone Secretion
    • Mineralocorticoid Receptors: Cloning
    • Mineralocorticoid Receptors: Characterization
    • Aldosterone Specificity-Conferring Mechanisms: Transcortin, 11βHSD2
    • Apparent Mineralocorticoid Excess
    • Extraepithelial Actions of Aldosterone
    • Aldosterone, Cardiac Hypertrophy, and Cardiac Fibrosis
    • Aldosterone: a Stress Hormone?
    • MR Activation and Stress
    • Primary Aldosteronism
    • Glossary
  • Chapter 22. Androgen Action and Stress
    • Androgens Major Forms of Androgens
    • The Androgen Receptor
    • Physiological Actions of Androgens
    • Androgen-Associated Pathology
    • Interactions Between Stress and Androgens
    • Summary
  • Chapter 23. Angiotensin—Encyclopedia of Stress
    • Components of the Renin–Angiotensin System
    • Alternative Enzymes
    • Endocrine Renin–Angiotensin System
    • Local Renin–Angiotensin Systems
    • Renin–Angiotensin System and Stress
  • Chapter 24. Stress, Angiotensin, and Cognate Receptors
    • Introduction
    • Components of the Classical RAS
    • Nonclassical Angiotensin Peptides
    • Receptors for Angiotensin Peptides
    • Neuroendocrine Actions of Angiotensin
    • Conclusions and Perspectives
  • Chapter 25. Annexin A1
    • Introduction
    • Structure of ANX-A1
    • The ANX-A1 Gene
    • Distribution of ANX-A1
    • Regulation of the Expression and Cellular Disposition of ANX-A1
    • The ANX-A1 Receptor
    • Functions of ANX-A1
    • ANX-A1–Derived Peptides
    • Summary
  • Chapter 26. Corticotropin-Releasing Factor Receptor Antagonists
    • Pharmacology of CRF/Urocortin Receptor Systems
    • Nonneuroendocrine Distribution of CRF1 Receptors
    • Selected CRF Receptor Antagonists
    • Therapeutic Potential of CRF1 Antagonists
    • Glossary
  • Chapter 27. Antidepressant Actions on Glucocorticoid Receptors
    • Introduction
    • HPA Axis and Glucocorticoid Receptors in Depression
    • Antidepressants Effects on Glucocorticoid Receptors
    • Conclusions
  • Chapter 28. Lipids and Lipoproteins
    • Introduction
    • Structure, Function, and Stability of Lipids and Lipoproteins
    • Environmental and Behavioral Influences on Lipid Concentrations and Lipid Variability
    • Chronic Psychological Stress
    • Acute and Episodic Psychological Stress
    • Mechanisms of Lipid Variability During Stress
    • Interventions to Reduce Stress-Related Increases in Lipid Concentrations
    • Clinical Implications of Variations in Lipid Concentrations
    • Future
  • Chapter 29. Corticosteroid Receptors
    • Introduction
    • Overall Structure
    • Receptor Variants
    • Finding Nuclear Targets
    • Transcriptional Regulation
    • Conclusion
  • Chapter 30. Glucocorticoid Receptor: Genetics and Epigenetics in Veterans With PTSD
    • PTSD as a Genetic Disorder
    • PTSD as an Epigenetic Disorder
    • Conclusion
  • Chapter 31. Stress Effects on Learning and Memory in Humans
    • Introduction
    • Definition of Stress
    • The Two Stress Systems: HPA and SNS
    • Stress and Cognition: Acute Effects
    • Stress and Cognition: Chronic Effects
    • Intervention Strategies
    • Outlook
  • Chapter 32. Sex Differences in Chronic Stress: Role of Estradiol in Cognitive Resilience
    • Introduction
    • Learning and Memory is Impaired in Males Following Chronic Stress
    • Learning and Memory is Enhanced in Females Following Chronic Stress
    • Role of Estrogens in Cognitive Resilience to Stress
    • Chronic Stress Increases Anxiety in Both Sexes
    • Chronic Stress Increases Depression in Male Rats
    • Sex Differences in Stress Effects on Neuronal Function
    • Conclusions and Possible Contributions of Sex Differences in the Stress Response and Estradiol to Mental Health
  • Chapter 33. Rapid and Slow Effects of Corticosteroid Hormones on Hippocampal Activity
    • Corticosteroids and the Brain
    • Rapid Effects on Neuronal Activity
    • Slow Effects on Neuronal Activity
    • Concluding Remarks
  • Chapter 34. 11β-Hydroxysteroid Dehydrogenases
    • Definition: 11β-Hydroxysteroid Dehydrogenase
    • Two Isozymes and a Solution to the Mineralocorticoid Receptor Paradox
    • 11β-HSD2 in the Adult CNS
    • 11β-HSD2 in the Developing CNS
    • 11β-HSD2 and Fetal Programming
    • Fetal Programming of the Hypothalamic-Pituitary-Adrenal Axis and Behavior
    • 11β-HSD1 in the Brain
    • 11β-HSD1 and the HPA Axis
    • 11β-HSD1 and Cognitive Aging
    • Conclusions
    • Glossary
  • Chapter 35. Stress, Insulin Resistance, and Type 2 Diabetes
    • Introduction
    • The Stress Response
    • Chronic Stress, Depression and Type 2 Diabetes
    • Obesity-Related Inflammation as a Chronic Stress State
    • Conclusion
  • Chapter 36. Steroid Hydroxylases
    • Introduction
    • Cholesterol Side-Chain Cleavage Enzyme: CYP11A1
    • 17-Hydroxylase: CYP17A1
    • 21-Hydroxylase: CYP21A2
    • 11β-Hydroxylases: CYP11B1 and CYP11B2
    • Aromatase: CYP19A1
    • Steroid Catabolism by Cytochrome P450s
  • Chapter 37. Manipulating the Brain Corticosteroid Receptor Balance: Focus on Ligands and Modulators
    • Introduction
    • Glucocorticoid Receptor Ligands and Modulators
    • Mineralocorticoid Receptor Ligands and Modulators
    • Human Studies with MR:GR Ligands and Modulators
    • Perspectives
  • Chapter 38. Stress and the Central Circadian Clock
    • Introduction
    • The Central Molecular Clock
    • Stress
    • Sites of Interaction Between the Circadian Clock System and the Stress System
    • Summary and Future Directions
  • Chapter 39. Nongenomic Effects of Glucocorticoids: Translation From Physiology to Clinic
    • Introduction
    • The Classical Genomic Mechanism of GC Actions and the Adverse Effects of GCs
    • The Nongenomic Effects of GC Actions Related to Clinical Usages
    • The Nongenomic Mechanism of GC Actions and Development of New Drugs
    • Conclusion

Part III. Diurnal, Seasonal, and Ultradian Systems

  • Chapter 40. Circadian Rhythm Effects on Cardiovascular and Other Stress-Related Events
    • Chronobiology and Circadian Rhythms
    • Stress and Circadian Rhythms
    • Stress and Individual Chronotype
    • Stress and Circadian Variation of Cardiovascular Events
    • Circadian Variation of Triggering Factors
    • A Novel Stress-Related Model of Cardiac Disease With Possible Circadian Variation: Takotsubo Cardiomyopathy
  • Chapter 41. Seasonal Variation in Stress Responses
    • Introduction
    • Seasonal Energetic Adaptations
    • Seasonal Adjustments in Glucocorticoid Secretion
    • Why Are Stress Responses Seasonally Variable?
    • Glossary
  • Chapter 42. Seasonal Rhythms
    • Evidence for Seasonal Glucocorticoid Rhythms
    • Evidence for Seasonal Rhythms Downstream of Glucocorticoid Release
    • Mechanisms Regulating Annual Rhythms of Glucocorticoids
    • Why Do Seasonal Glucocorticoid Rhythms Exist?
    • Avian Migration: Testing Seasonal Glucocorticoid Rhythm Hypotheses
    • Adaptive Significance
    • Importance for Biomedical Research
  • Chapter 43. Ultradian Rhythms
    • Introduction
    • Ultradian Rhythm of the HPA Axis
    • The Origin and Regulation of Glucocorticoid Pulsatility
    • Importance of Pulsatility for Gene Expression and Behavior
    • Clinical Relevance of Pulsatility


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© Academic Press 2017
15th December 2016
Academic Press
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About the Editor

George Fink

George Fink

Dr. Fink is Honorary Professor in the University of Melbourne and Professorial Research Fellow at the Florey Institute of Neuroscience and Mental Health. Formerly, he was Scientific Director of the Mental Health Research Institute, Melbourne, Australia. Before returning to Melbourne in 2003, Dr. Fink was University Lecturer in Human Anatomy and Fellow in Physiology and Medicine at Brasenose College and the University of Oxford and served for nearly 20 years as CEO and Director of the UK Medical Research Council’s Brain Metabolism Unit in Edinburgh. He gained distinction through his seminal research discoveries in neuroendocrinology and psychopharmacology published in over 360 scientific papers. Dr. Fink served as President of the European Neuroendocrine Association. His distinctions include Fellow of the Royal Society of Edinburgh, Fellow of the Royal College of Physicians of Edinburgh, Fellow of the Royal Biological Society, Fellow of the Physiological Society, and Honorary Member of the British Society for Neuroendocrinology. Fink was Honorary Professor in the University of Edinburgh, delivered the inaugural Geoffrey Harris Prize Lecture of the British Physiological Society, and the Wolfson Lecture. In 1979 he was awarded the Royal Society - Israel Academy Exchange Fellowship which enabled him to spend a research year at the Weizmann Institute of Science, Rehovot Israel. In 2000 he was awarded the Lifetime Achievement Award of the International Society of Psychoneuroendocrinology. His membership of learned societies includes Emeritus member of the Society for Neuroscience, the Endocrine Society and the Genetics Society of America. Dr. Fink has edited several scientific books with Elsevier, including Stress Science: Neuroendocrinology (2009), Stress Consequences: Mental, Neuropsychological and Socioeconomic (2009), Stress of War, Conflict and Disaster (2010), the Handbook of Neuroendocrinology (2011), and most notably the 4-volume second edition of the Encyclopedia of Stress (2007) on which this new Handbook of Stress series is based. He was founding Editor-in-Chief of the first edition of the Encyclopedia of Stress (2000) which was awarded the 2001 British Medical Association commendation for its contribution to Mental Health. The first volume of his Handbook of Stress series, entitled “Stress: Concepts, Cognition, Emotion, and Behavior”, received the BMA High Commendation in the Health and Social Care category as one of the top titles in its discipline.

Affiliations and Expertise

Professorial Research Fellow and Hon Professor, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia

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