Astrocytes in Psychiatric Disorders (Advances in Neurobiology, 26)

This contributed volume discusses the multiple roles of astrocytes, which determine the progression and outcome of neuropsychiatric diseases. This emerging area of study examines the ways in which astrocytes are involved in various aspects of disease initiation, progression and resolution. This monograph aims to integrate the body of information that has accumulated in recent years revealing the active role of astrocytes in neuropsychiatric pathology and in psychiatric disorders. Understanding roles of astrocytes in pathology will provide new targets for medical intervention and aid the development of much needed therapeutics. This book will be valuable for researchers and workers in the fields of neurobiology, neurology, and psychiatry, as well as fill the need for a textbook used in advanced courses/graduate seminars in glial pathophysiology. Contents 6 Part I: General Aspects of Astrogliopathology with Emphasis on Neurocognitive Disorders 8 Neuroglia in Psychiatric Disorders 9 Introduction: Definition, Classification, and Main Functions of Neuroglia 9 Microglia 11 Oligodendrocyte and NG-2 Glia 12 Astrocytes 13 Astrogliopathology in Neuropsychiatric Disorders 16 Reactive Astrogliosis in Neuropsychiatric Disorders 17 Astrocyte Degeneration, Atrophy, and Loss of Function in Neuropsychiatric Disorders 18 Astrocyte Pathological Remodeling in Cognitive Disorders 18 Envoi 19 References 19 Astrocytes: The Housekeepers and Guardians of the CNS 26 Astroglia: Definition and Evolutionary Origins 26 Types of Astroglia 27 Protoplasmic Astrocytes 27 Fibrous Astrocytes 29 Juxtavascular Astrocytes 29 Surface-Associated Astrocytes 30 Velate Astrocytes 30 Radial Astrocytes 30 Interlaminar and Varicose Projection Astrocytes in the Primate Brain 30 Physiology of Astrocytes 31 Ion Channels 31 Receptors of Neurotransmitters 35 Astroglial Plasma Membrane Transporters 36 Intracellular Excitability of Astrocytes 38 Astrocyte Ca2+ Excitability 38 Sodium Signalling 40 Astrocyte Functions 41 Ion Homeostasis in the CNS, or Ionostasis 42 Neurotransmitter Homeostasis 44 Astroglial Cradle in Regulation of Synaptic Transmission 45 Astrocytes Protect Nervous Tissue Against Reactive Oxygen Species 47 Neurogliovascular Unit and the Blood-Brain Barrier 47 Astrocytes and Gliotransmission 48 Astrocytes and the Glymphatic System 49 Envoi 49 References 49 Principles of Astrogliopathology 59 Pathological Potential of Neuroglia 59 Astrogliopathology: General Principles 60 Reactive Astrogliosis 61 Pathological Remodelling of Astrocytes 65 Astroglial Atrophy, Asthenia and Loss of Function 66 Astrodegeneration or Clasmatodendrosis 70 Envoi 70 References 71 Morphological Features of Astrocytes in Health and Neuropsychiatric Disorders 78 Introduction 78 Astrocyte Morphological Heterogeneity 79 Astrocyte Molecular Heterogeneity 83 Morphological Changes in Neuropsychiatric Disorders 85 Major Depressive Disorder 85 Schizophrenia and Bipolar Disorder 90 References 91 Part II: Astroglia in Mood Disorders 96 Astrocytes in Bipolar Disorder 97 Introduction 97 Neuropathology of BD 100 Astrocyte Changes in BD 101 Astroglial Glutamate Regulation in BD 102 Astrocytes and Disruption of Circadian Rhythms in BD 103 Astrocytes and Altered Metabolism in BD 104 Lithium-Responsive Astroglial Gene Networks 105 Conclusions 107 References 107 Astroglia Abnormalities in Post-stroke Mood Disorders 116 Overview of Stroke 116 Pathological Processes of Ischemic Stroke 118 Acute Responses and Cell Death After Ischemic Stroke 118 Astrocytes and Reactive Astrogliosis After Ischemic Stroke 121 Post-stroke Symptoms and Post-stroke Mood Disorder (PSMD) 123 Astrocytes in Major Depressive Disorder (MDD) and PSMD 125 Astrocyte in MDD 125 Studies from Human Postmortem Brain Specimens 125 Studies from Animal Models 127 Astrocytes in PSMD 131 Concluding Remarks 133 References 133 Astroglia and Obsessive Compulsive Disorder 140 Introduction 140 Astrocytic Glutamate Transporter GLT1-Deficient Mice Exhibit Pathological Repetitive Behaviors 141 GLT-1 Loss in C. elegans Drives Repetitive Behavior Through Presynaptic Activation of mGluR5 143 Reduced Astrocyte Calcium Signaling Produces Abnormal Repetitive Behavior via Functional Upregulation of Astrocytic GABA Transporter GAT-3 144 Conclusion 146 References 146 Part III: Astroglia in Schizophrenia 151 Astrocytes in Neuropsychiatric Disorders: A Review of Postmortem Evidence 152 Introduction 152 Postmortem Changes in Astrocytes in Schizophrenia (SCZ) 154 Postmortem Changes in Astrocytes in Major Depressive Disorder (MDD) 157 Postmortem Changes in Astrocytes in Bipolar Disorder (BPD) 159 Factors That Affect Astrocytes in Postmortem Studies of Neuropsychiatric Disorders 162 Effects of Psychotropic Medications on Astrocytes in Postmortem Tissue 164 References 165 Astrocyte Bioenergetics and Major Psychiatric Disorders 172 Introduction 172 Metabolite-Mediated Interorgan Signaling 173 Regulation of Vascular Energy Supply 175 Metabolic Fluxes in Gray Matter 177 Pathways of Nutrient Utilization 178 Intercellular Transport of Metabolites 179 Flux Redistribution in Response to Demand 180 Metabolic Disorders and Neuropsychiatric Disorders 183 Postmortem Evidence 183 Genetic Evidence 184 Gene Expression and Functional Data 185 Effects of Antipsychotic Medications 186 Insights from Animal Models 187 Pharmacological Models 187 Neuroinflammatory Models 189 Clues from Models of Substance Use Disorders 191 Genetic Models 193 Therapeutic Possibilities 197 Outlook 198 References 199 Part IV: Astroglia in Addictive Disorders 227 Astrocytes in Addictive Disorders 228 Overview of Addiction Biology 228 Circuitry and Transmitters 228 Transmitter Uptake 230 Glutamate 230 GABA 232 Dopamine 233 Gliotransmission 234 Glutamate 234 D-Serine 236 ATP 237 Synaptic Proximity 238 Morphological Plasticity of Astrocytes 238 Impact of Synaptic Insulation on Synapse Function 239 Drug-Induced Morphological Plasticity 240 Homeostatic Functions 240 Synaptogenesis 240 Network Homeostasis 241 Conclusions 242 References 242 Astroglia in the Vulnerability and Maintenance of Alcohol Use Disorders 252 Introduction 252 Molecular Pathology of Astrocytes in Alcohol Use Disorders 253 Neuropathology of Astrocytes in Alcohol-Related Neurological Disorders 253 Alcohol Effects on Glutamate Receptors and Astrocyte Components of the Cycle for Release and Reuptake of Glutamate 256 AUDs and the Role of NMDA-Type Glutamate Receptors 257 AUDs and the Release of NMDA Receptor Co-agonists by Astrocytes 257 Astrocytic Glutamate and GABA Transporters and Glutamine Synthetase in the Vulnerability to Alcohol Abuse 258 Gap Junctions of Astrocytes in AUDs 259 Involvement of Astrocytes in Neuroimmune Responses Elicited by Alcohol Exposure 260 Astrocyte Thrombospondin in AUD-Related Synaptic Alterations 260 Astrocyte Processes at the Blood-Brain Barrier and the Involvement of Aquaporins in AUD-Related Neuropathology 261 Epigenetic Changes in Astrocytes in AUDs 262 Astrocyte Epigenetic Markers 262 Variety of Mechanisms Involving Astrocytes in the Vulnerability to AUDs 264 Effects of Early Alcohol Exposure and Stress on Astrocyte and Their Role in AUDs 266 References 267 Part V: Astroglia in Eating Disorders 277 Brain Volume Loss, Astrocyte Reduction, and Inflammation in Anorexia Nervosa 278 Introduction 278 Brain Volume Reduction 279 Potentially Underlying Pathophysiology of Brain Volume Loss and the Role of Astrocytes 280 The Origin of Astrocyte Loss in AN 283 Potential Functional Consequences of Astrocyte Loss 283 Astroglia as Targets for Gonadal Steroid Hormones 284 Inflammation in AN and the Role of Astrocytes 288 Inflammation in AN 289 Astrocytes and Inflammation in the CNS 290 Astrocytes and Metabolic Diseases 291 The Hungry Astrocyte In Vitro 291 Astrocytes in Animal Models of AN 293 Gut Microbiota Alterations in AN and the Influence on Astrocytes 293 The Microbiome: General 293 The Microbiome: Anorexia Nervosa Animal Model 295 The Microbiome: Astrocytes 296 Conclusion and Outlook 297 References 298 Part VI: Targeting Astrocytes in Therapeutic Management of Neuropsychiatric Disorders 309 Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants 310 Introduction 310 Serotonin Receptors in the Treatments of MDD 312 5-HT1 Receptors 312 5-HT2 Receptors 314 Other Serotonin Receptors 318 Astrocytes as a Target for Classic Antidepressants 319 SSRIs 320 SNRIs 323 TCAs and MAOIs 324 Astrocytes in Treatments of Bipolar Disorders 324 Conclusion 326 References 327 Ketamine Action on Astrocytes Provides New Insights into Rapid Antidepressant Mechanisms 341 Astrocytes and Mood Disorders 341 Impact of Antidepressants on Astrocytes 342 Ketamine: The Fastest Acting Antidepressant 343 Ketamine Increases Astrocyte cAMP and Alters Single Vesicle Interactions with the Plasmalemma 344 Ketamine Induces Cholesterol Redistribution in the Astrocyte Plasmalemma 347 Ketamine Attenuates Mobility of Vesicles Delivering Kir4.1 349 References 351 Epilogue 358 Index 360