Stress: Physiology, Biochemistry, and Pathology: Handbook of Stress Series, Volume 3

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STRESS: PHYSIOLOGY, BIOCHEMISTRY, AND PATHOLOGY
Copyright
Contributors
Preface
1. Arousal
	Evidence for the Existence of GA
	Physical and Quantitative Properties of GA
	Neurologic Maladies and Public Health Problems From Dysregulation of GA
	Neurons Critical for GA
	Arousal and Psychiatric Disorders
	Psychiatric Disorders Associated With Hyperarousal
	Conditions Featuring Arousal Dysregulation
	Psychiatric Disorders Associated With Hypoarousal
	Summary
	References
2. Resilience of the Brain and Body
	Introduction
		Brain-Body Basics
		Central Role of the Brain
		Plasticity of the Adult and Developing Brain
		Stress-Induced Structural Plasticity
		Epigenetics
		Brain Gene Expression Is Continually Changing
		Development of the Capacity for Resilience
		How the Brain Gets “Stuck”
		Prevention
		Neurobiological Mechanisms of Overcoming Loss of Resilience
		Some Examples of Opening Windows to Promote Resilience
		Other Top-Down Therapies That Change the Brain
	Conclusion
	References
3. Cerebral Metabolism, Brain Imaging and the Stress Response
	Introduction
	Imaging the Stress Response Using the Example of Posttraumatic Stress Disorder
		Resting State Brain Function in Humans
		Brain Function During Flashbacks, After Traumatic Reminders and Alleviating Interventions
			Effects of Mindfulness
			Pharmacological Interventions
			Limbic-Hypothalamic-Pituitary-Adrenal Axis
			Road Traffic Accidents
			Alternative Activation Strategies
		Pharmacological Imaging
			Dopamine
			Serotonin
			Cannabinoid Receptor
			Glutamate Receptor
		Stress Mechanisms in the Etiology of Other Psychiatric Disorders
	Chronic Stress and Its Effect on Structural In Vivo Brain Imaging
		Early Life Stress
		Everyday Stress
	Future Developments
	References
4. Stress-Hyporesponsive Period
	Introduction
	Stress-Hyporesponsive Period
	SHRP, the Adrenal and Corticosterone
	SHRP and the Pituitary
	SHRP and the Brain
	Corticosteroid Feedback
	Conclusion
	References
5. Hippocampus and Hippocampal Neurons∗
	Overview
	Hippocampal Formation
	Laminar Organization
	Cross-Sectional Organization—Trisynaptic Circuit
	Principal Neurons
	Interneurons
	Intrinsic and Extrinsic Neural Connections
	Neurochemistry
		Amino Acid Neurotransmitters
		Biogenic Amines
		Other Neuromodulators
	Neuroplasticity
		Hippocampal Function
	References
6. Memory and Stress
	STRESS
	IMPORTANT FACTORS TO CONSIDER WITH REGARDS TO METHODOLOGY
		Modulation of Stress Hormones
		Valence of the To-Be-Remembered Material
	IMPACT OF STRESS ON MEMORY
		Impact of Stress on Memory Encoding and Memory Consolidation
		Impact of Stress on Memory Retrieval
		Impact of Stress on Reactivated Memories and Memory Reconsolidation
	IMPLICATIONS FOR TRAUMATIC MEMORIES
	INSIGHTS FOR FUTURE STUDIES
	References
7. Adult Neurogenesis and Stress
	Introduction
	Species Differences in Adult Hippocampal Neurogenesis
	Stress Effects on Adult Neurogenesis
	A Role for Stress Hormones in Adult Neurogenesis
	Sex Differences in Stress-Induced Changes in Adult Neurogenesis
	Function of Stress-Induced Changes in Adult Neurogenesis
	Conclusions
	References
8. Stress, Corticosterone, and Hippocampal Plasticity
	Introduction
	Induction of Stress
	Molecular Mechanisms
	Network Mechanisms
	Conclusions
	References
9. Dopamine and Stress
	Introduction
	Nerve Cells, Synaptic Transmission, and DA Pathways in the CNS
		Responses of Dopaminergic Systems to Acute Stressful Stimuli
		Responses of Dopaminergic Systems to Chronic Stress
	Interactions Between DA and Other Neurochemical Systems Altered by Stress
		DA and the HPA Axis
		DA and Excitatory Amino Acids
		DA and NE
		DA and Serotonin
		DA and DA
		Developmental Modulation
	References
10. Serotonin in Stress
	Introduction: Stress, Serotonin, and Human Psychopathology
	Effect of Stress on Serotonin Parameters in the Brain
		Animal Models
		Human Imaging
	Effect of Serotonergic Drugs on Stress Responses: Serotonin and HPA Axis Activity
		Animal Models
		Human Studies
	Stress, Serotonin, and Human Psychopathology
		Anxiety, PTSD, and Depression
		Psychoses
	Conclusions
	References
11. Excitotoxicity
	Introduction
	Excitotoxic Mechanisms
	Evidence That Physiological and Psychological Stress Can Endanger Neurons
	Stress Hormones and Excitotoxicity
	Ketone Bodies and Resistance to Excitotoxicity
	Excitoprotective Effects of Mild Neuronal Stress
	Environmental and Genetic Risk Factors for Stress-Mediated Excitotoxic Neuronal Degeneration
	References
12. Chaperone Proteins and Chaperonopathies
	Objectives and Scope
	Chaperones and the Chaperoning System
	Chaperonopathies
	Structural Hereditary Chaperonopathies
		sHsp Chaperonopathies
		Hsp60 and CCT Chaperonopathies
		Hsp40(DnaJ), Hsp70(DnaK), and Super Heavy Chaperones
		Chaperonopathies Associated With Abnormal Organelle Chaperones
		Chaperonopathies Associated With Dedicated Chaperones
	Gene Polymorphisms and Chaperonopathies
	Chaperonopathies Attributable to Chaperone-Gene Dysregulation
	Other Types of Chaperonopathies
	Chaperones and Metabolic Pathways
	Acquired Chaperonopathies
		Autoimmunity and Chronic Inflammation
		Carcinogenesis
		Indeterminate Clinical Pictures Which Could Implicate Chaperonopathies
	Chaperonotherapy
	Conclusions and Perspectives
	Acknowledgments
	References
13. Oxidative Stress: Eustress and Distress in Redox Homeostasis
	Introduction
	Concept of Oxidative Stress
		Brief Historical Remarks
		Oxidative Eustress and Oxidative Distress
	Adaptive Oxidative Stress Responses
		Hormesis
	Kinds of Oxidative Stress
		Nutritional Oxidative Stress
		Postprandial Oxidative Stress
		Photooxidative Stress
		Radiation-Induced Oxidative Stress
		Reductive Stress
		Nitroxidative, Nitrosative, Nitrative Stress
	Oxidant Sources
		Endogenous (Cellular) Oxidant Sources
		Exogenous Oxidant Sources: Exposome
	Consequences in Health and Disease
	Some Current Lines of Development
		Relation to Calcium Signaling
		Toxicology
		Stress Response
		Circadian Rhythm
		Aging
		Plant Research
		Medical (Small Sample of Extensive Current Activity)
		Environment
	Concluding Remarks
	Acknowledgments
	References
14. Gender and Stress
	Evidence Supporting Sex Differences in Stress Responses
		Sex Differences in Adrenal Function
		Sex Differences in Neuroendocrine Function
			Pituitary Hormone Secretion
		Hypothalamic Function
		Negative Feedback Regulation
		Sex Differences in Behavioral Responses to Stress
	Basic Mechanisms of Sexual Differentiation of Neural Function
		Organizational Effects of Gonadal Steroid Hormones on Stress Responses
		Activational Effects of Gonadal Steroid Hormones on Stress Responses
	Clinical Implications for Gender Differences in Stress Responses
	References
15. Atrial Natriuretic Peptide, the Hypothalamic–Pituitary–Adrenal Axis, and Panic Attacks
	Introduction
	The NPs System
	NPs and the HPA System
	Effects on Anxiety and Panic Attacks
	Outlook
	References
16. Stress, Reward, and Cognition in the Obese Brain
	Introduction: Stress, Appetite, and Control
	Stress, Craving, and Motivational/Affective Biases in Obesity
	Stress and Cognition in Obesity
	Stress and Brain Function and Structure in Obesity
	Conclusions
	References
17. The Innate Alarm System: A Translational Approach
	Introduction
	Innate Defense Responses in Animals
		The Defense Cascade Model
	Innate Defense Responses in Humans
	The Innate Alarm System
	Conscious and Subconscious Processing of Threat in PTSD
		Conscious Threat Processing in PTSD
		Subconscious Threat Processing in PTSD
		PTSD Symptomatology and the IAS During Threat Processing
		Functional Connectivity of Brain Regions Associated With the IAS in PTSD
		The Role of the Amygdala in Innate Defensive Responding in PTSD
		Brainstem Regions and Innate Defensive Responding in PTSD
	Clinical and Research Implications
	Acknowledgments
	References
18. Stress-Induced Anovulation
	Definitions
	Introduction
		Neuroendocrine Mechanisms Linking Cognition, Mood, Behavior, and GnRH Drive
		Pathogenesis of Stress-Induced Anovulation
		Behavioral, Nutritional, and Metabolic Influences on the Reproductive Axis
	Behavioral Influences
		Nutritional and Metabolic Influences
	Synergism Among Stressors
	Treatment Considerations
	Acknowledgments
	References
19. Multidrug Resistance P-Glycoprotein (P-gb), Glucocorticoids, and the Stress Response
	Introduction
	P-glycoprotein: An Overview
		P-gp Substrates
	P-gp Localization and Regulation
		Blood–Brain Barrier
		Other Brain Regions
		Pituitary and Adrenal Gland
		Glucocorticoid Excretion
	Stress-Related Substrates and HPA Function
	P-gp and Development
		Placenta
		Fetal Blood-Brain Barrier
	Concluding Remarks
	Disclosure
	Acknowledgments
	References
20. Stress and Glucocorticoids as Experience-Dependent Modulators of Huntington's Disease
	Introduction
	Modeling Huntington's Disease in Mice
		Glucocorticoids and the Stress Response
		Mechanisms of Stress-Induced Changes
		The Effects of Stress Depend on Many Variables
		Stress Paradigms Used in Rodents
			Corticosterone in Drinking Water
			Restraint Stress
			Chronic Unpredictable Stress
			Social Defeat and Predator Exposure
		Stress in Neurological and Psychiatric Disorders
		Stress in Huntington's Disease
			Psychological Stress
			Abnormal Stress Response
	The Effects of Stress and Stress Hormone Inventions in HD Mice
		Oral CORT Treatment
	Corticosterone Treatment Accelerated the Onset of Y-Maze Memory Deficits in Male HD Mice
		Prolonged CORT Treatment–Induced Anhedonia Only in Female Mice
		Motor Coordination Was Unaffected by CORT Treatment
		Reduced Hippocampal MR Levels in R6/1 Mice at a Young Age
	The Effects of Elevated Corticosterone Treatment on Novel Behavioral Phenotypes in HD Mice
		Two Weeks of CORT Treatment Impaired Olfactory Sensitivity in Female Mice
		CORT Treatment–Enhanced Female Social Interaction in Male R6/1 and WT Mice
	The Effects of Chronic Restraint Stress on the HD Phenotype
		Chronic Restraint After 9 weeks Is Still “Stressful”
		Response to Chronic Stress Between the Genotypes
		Restraint Enhanced Rotarod Performance and Induced HyperLocomotion in Male Mice
		Sex Difference in Restraint-Induced Rotarod Effect
		Restraint Transiently Reduced Saccharin Preference and Nest Quality in Female WT Mice
		Olfactory Sensitivity Is Modulated by Restraint and the HD Mutation
			Olfactory Deficits in Female R6/1 Mice Were More Vulnerable to 2 Weeks of Restraint Stress Compared to WT Littermates
			Olfactory Sensitivity Deficits in Male Mice Were Impaired by Restraint Stress
	Stress as a Novel Environmental Modulator of HD
		Future Directions
	Conclusions
	References
	Further Reading
21. PACAP: Regulator of the Stress Response
	Introduction to Pituitary Adenylate Cyclase–Activating Polypeptide
		Discovery, Characterization, and Evolution
		General Functions
		Distribution
	PACAP Receptors
		Receptor Characterization
		Associated Pathways
		Receptor Agonists and Antagonists
	Uncovering PACAP as a Stress Peptide: The Role of Functional Genomics
	PACAP Regulation of the Autonomic Nervous System
		The Primary Neurotransmitter at the Sympathetic Adrenomedullary Synapse
		PACAP's Role in the SNS Outside of the Sympathetic Adrenomedullary Axis
			Regulation of Pre- and Post-Ganglionic Sympathetic Nerve Activity
			Central Regulation of the SNS
	PACAP and the Hypothalamic–Pituitary–Adrenal Axis
		Regulation of the HPA Axis
		Extrahypothalamic Regulation of the HPA Axis
	PACAP in the Pathophysiology of Stress Disorders: A Maladaptive Response to Stress
		PACAP's Sex-Specific Association With PTSD Risk: Clinical Association and Mechanistic Evidence
	Summary
	Conflicts of Interest
	References
22. Glucose Transport
	Introduction
		Glucose Transporter Proteins
		Glucose Transport
		Overview of Glucose Transport Regulation
		Stress Hormones and Glucose Transport
		GLUTs as Stress-Responsive Proteins
		Metabolic Stresses and Glucose Transport
			Hypermetabolism
			Mitochondrial Inhibitors
			Glucose Deprivation
		Obesity, Type 2 Diabetes Mellitus, and Cardiovascular Disease
		Overall Effects of Transport Regulation
		Signaling Cascades and Glucose Transport
		GLUTs, Glucose Transport, and Metabolism in Chronic Disease States—Cancer
	Summary
	Acknowledgments
	References
23. Links Between Glucocorticoid Responsiveness and Obesity: Involvement of Food Intake and Energy Expenditure
	Introduction
	Nexus Between Body Weight, Obesity and Activation of the HPA Axis
	Physiological Determinants of Glucocorticoid Responsiveness: Selection of LR and HR Individuals
	Cortisol Responsiveness and Innate Predisposition to Weight Gain
	Cortisol Responsiveness and the Neural Control of Food Intake
	Cortisol Responsiveness and Thermogenesis
	Neuroendocrine Determinants of Altered Thermogenesis in LR and HR
	Cortisol Responsiveness, Coping Strategies, and Physical Activity
		Future Perspective
	References
24. Blood–Brain Barrier: Effects of Inflammatory Stress
	Introduction
	Structure and Function of the Blood–Brain Barrier
		Physical Barrier
		Functional Barrier
		The Metabolic and Enzymatic Barrier
		The Neurovascular Unit
	Neuroinflammation and BBB Physiology
		BBB Integrity Impairment and Immune Cell Trafficking
		Regulation of Transport Activities
		Inflammatory Modulation of Metabolism
	Inflammatory Stress at the BBB in Pathological Contexts
		Neurodegenerative Diseases
		Hypoxia-Ischemia Brain Injury and Stroke
		Epilepsy
		Infectious Diseases
		Diabetes
	Conclusions
	Acknowledgments
	References
25. Blood–Brain Barrier in Alzheimer's Disease
	Introduction
	Blood–Brain Barrier
	BBB Characteristics
	BBB Constitution
	Neurovascular Unit
	BBR Dysfunction in AD
	AD Pathogenesis
	Disruption of Barrier Properties in AD
	Dysregulation of Transport Systems in AD
	Concluding Remarks
	Acknowledgments
	References
26. Thermal Stress and Its Physiological Implications
	Introduction
		Exogenous and Endogenous Sources of Thermal Stress
		Climate Change and the Speciation of Homo Sapiens
		Generalisations Concerning Thermal Stress
	Our Thermal Environment
		First Principles
			Stress and Strain in the Human Thermal Context
			The Thermal and Water Vapour Pressure Continua
			Thermodynamics
			The Impact of Composition and Shape on Heat Exchanges
		Quantification of the Thermal Environment
			Indices of Stress and Strain
	Concepts of Mammalian Homoeothermy
		Morphological Considerations
			The Cutaneous Vascular Network
			Eccrine Sweat Gland Distributions
			Skeletal Muscles
		Principles of Physiological Control and Regulation
			Passive and Active Systems
			Homoeostasis
			Normothermia, Physiological Accommodation, and Zones of Thermoregulation
			Thermal Adaptation
			Thermally Mediated Cutaneous Vasomotor Responses
			Thermally Mediated Sudomotor Responses
			Morphological Determinants of Cutaneous Blood Flow and Sweating
			Predicting Scenarios of Adverse Strain
	Interactive Influences
		Interactions With Other Homoeostatic Mechanisms
		Nonthermal Sudomotor Responses: Psychological Stress
		The Interactive Impact of Clothing
	Conclusion
	Acknowledgments
	References
27. Stress and Salt Appetite
	Stress-Induced Salt Appetite in Animals
	ACTH-Induced Salt Appetite
	Hormones Influencing Salt Appetite in Stressed Animals
		Adrenocorticotropic Hormone
	Renin, Angiotensin, Aldosterone
	The Effects of Increased Sodium Levels on Stress and Anxiety
	Stress and Human Salt Appetite
	References
28. Central Mechanisms Generating Cardiovascular and Respiratory Responses to Emotional Stress
	Introduction
	Pattern of Cardiovascular and Respiratory Responses Associated With Emotional Stress
	Key Brain Regions Activated by Emotional Stress
		DMH/PeF Region
		Amygdaloid Complex
		Midbrain PAG
		Medial Prefrontal Cortex
	Summary and Conclusions
	References
29. Febrile Response and Seizures
	Fever and Seizures
	Causative Factors Mediating Seizures Caused by Fever
		Genetic Susceptibility
		Increased Brain Temperature Affects Permeability of the Ion Channels
		The Role of the Innate Immune System
			Clinical Studies
			Experimental Studies
		Alkalosis and FS
		Potassium Chloride Cotransporter
	FSs and Epilepsy: Human and Animal Studies
	FSs and Cognitive Dysfunction
	Implications for Therapy
	References
Index
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	B
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	D
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	U
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	W
	X
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	Z
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