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.
Author(s): Baoman Li, Vladimir Parpura, Alexei Verkhratsky, Caterina Scuderi
Series: Advances in Neurobiology, 26
Publisher: Springer
Year: 2021
Language: English
Pages: 383
City: Cham
Contents
Part I: General Aspects of Astrogliopathology with Emphasis on Neurocognitive Disorders
Neuroglia in Psychiatric Disorders
Introduction: Definition, Classification, and Main Functions of Neuroglia
Microglia
Oligodendrocyte and NG-2 Glia
Astrocytes
Astrogliopathology in Neuropsychiatric Disorders
Reactive Astrogliosis in Neuropsychiatric Disorders
Astrocyte Degeneration, Atrophy, and Loss of Function in Neuropsychiatric Disorders
Astrocyte Pathological Remodeling in Cognitive Disorders
Envoi
References
Astrocytes: The Housekeepers and Guardians of the CNS
Astroglia: Definition and Evolutionary Origins
Types of Astroglia
Protoplasmic Astrocytes
Fibrous Astrocytes
Juxtavascular Astrocytes
Surface-Associated Astrocytes
Velate Astrocytes
Radial Astrocytes
Interlaminar and Varicose Projection Astrocytes in the Primate Brain
Physiology of Astrocytes
Ion Channels
Receptors of Neurotransmitters
Astroglial Plasma Membrane Transporters
Intracellular Excitability of Astrocytes
Astrocyte Ca2+ Excitability
Sodium Signalling
Astrocyte Functions
Ion Homeostasis in the CNS, or Ionostasis
Neurotransmitter Homeostasis
Astroglial Cradle in Regulation of Synaptic Transmission
Astrocytes Protect Nervous Tissue Against Reactive Oxygen Species
Neurogliovascular Unit and the Blood-Brain Barrier
Astrocytes and Gliotransmission
Astrocytes and the Glymphatic System
Envoi
References
Principles of Astrogliopathology
Pathological Potential of Neuroglia
Astrogliopathology: General Principles
Reactive Astrogliosis
Pathological Remodelling of Astrocytes
Astroglial Atrophy, Asthenia and Loss of Function
Astrodegeneration or Clasmatodendrosis
Envoi
References
Morphological Features of Astrocytes in Health and Neuropsychiatric Disorders
Introduction
Astrocyte Morphological Heterogeneity
Astrocyte Molecular Heterogeneity
Morphological Changes in Neuropsychiatric Disorders
Major Depressive Disorder
Schizophrenia and Bipolar Disorder
References
Part II: Astroglia in Mood Disorders
Astrocytes in Bipolar Disorder
Introduction
Neuropathology of BD
Astrocyte Changes in BD
Astroglial Glutamate Regulation in BD
Astrocytes and Disruption of Circadian Rhythms in BD
Astrocytes and Altered Metabolism in BD
Lithium-Responsive Astroglial Gene Networks
Conclusions
References
Astroglia Abnormalities in Post-stroke Mood Disorders
Overview of Stroke
Pathological Processes of Ischemic Stroke
Acute Responses and Cell Death After Ischemic Stroke
Astrocytes and Reactive Astrogliosis After Ischemic Stroke
Post-stroke Symptoms and Post-stroke Mood Disorder (PSMD)
Astrocytes in Major Depressive Disorder (MDD) and PSMD
Astrocyte in MDD
Studies from Human Postmortem Brain Specimens
Studies from Animal Models
Astrocytes in PSMD
Concluding Remarks
References
Astroglia and Obsessive Compulsive Disorder
Introduction
Astrocytic Glutamate Transporter GLT1-Deficient Mice Exhibit Pathological Repetitive Behaviors
GLT-1 Loss in C. elegans Drives Repetitive Behavior Through Presynaptic Activation of mGluR5
Reduced Astrocyte Calcium Signaling Produces Abnormal Repetitive Behavior via Functional Upregulation of Astrocytic GABA Transporter GAT-3
Conclusion
References
Part III: Astroglia in Schizophrenia
Astrocytes in Neuropsychiatric Disorders: A Review of Postmortem Evidence
Introduction
Postmortem Changes in Astrocytes in Schizophrenia (SCZ)
Postmortem Changes in Astrocytes in Major Depressive Disorder (MDD)
Postmortem Changes in Astrocytes in Bipolar Disorder (BPD)
Factors That Affect Astrocytes in Postmortem Studies of Neuropsychiatric Disorders
Effects of Psychotropic Medications on Astrocytes in Postmortem Tissue
References
Astrocyte Bioenergetics and Major Psychiatric Disorders
Introduction
Metabolite-Mediated Interorgan Signaling
Regulation of Vascular Energy Supply
Metabolic Fluxes in Gray Matter
Pathways of Nutrient Utilization
Intercellular Transport of Metabolites
Flux Redistribution in Response to Demand
Metabolic Disorders and Neuropsychiatric Disorders
Postmortem Evidence
Genetic Evidence
Gene Expression and Functional Data
Effects of Antipsychotic Medications
Insights from Animal Models
Pharmacological Models
Neuroinflammatory Models
Clues from Models of Substance Use Disorders
Genetic Models
Therapeutic Possibilities
Outlook
References
Part IV: Astroglia in Addictive Disorders
Astrocytes in Addictive Disorders
Overview of Addiction Biology
Circuitry and Transmitters
Transmitter Uptake
Glutamate
GABA
Dopamine
Gliotransmission
Glutamate
D-Serine
ATP
Synaptic Proximity
Morphological Plasticity of Astrocytes
Impact of Synaptic Insulation on Synapse Function
Drug-Induced Morphological Plasticity
Homeostatic Functions
Synaptogenesis
Network Homeostasis
Conclusions
References
Astroglia in the Vulnerability and Maintenance of Alcohol Use Disorders
Introduction
Molecular Pathology of Astrocytes in Alcohol Use Disorders
Neuropathology of Astrocytes in Alcohol-Related Neurological Disorders
Alcohol Effects on Glutamate Receptors and Astrocyte Components of the Cycle for Release and Reuptake of Glutamate
AUDs and the Role of NMDA-Type Glutamate Receptors
AUDs and the Release of NMDA Receptor Co-agonists by Astrocytes
Astrocytic Glutamate and GABA Transporters and Glutamine Synthetase in the Vulnerability to Alcohol Abuse
Gap Junctions of Astrocytes in AUDs
Involvement of Astrocytes in Neuroimmune Responses Elicited by Alcohol Exposure
Astrocyte Thrombospondin in AUD-Related Synaptic Alterations
Astrocyte Processes at the Blood-Brain Barrier and the Involvement of Aquaporins in AUD-Related Neuropathology
Epigenetic Changes in Astrocytes in AUDs
Astrocyte Epigenetic Markers
Variety of Mechanisms Involving Astrocytes in the Vulnerability to AUDs
Effects of Early Alcohol Exposure and Stress on Astrocyte and Their Role in AUDs
References
Part V: Astroglia in Eating Disorders
Brain Volume Loss, Astrocyte Reduction, and Inflammation in Anorexia Nervosa
Introduction
Brain Volume Reduction
Potentially Underlying Pathophysiology of Brain Volume Loss and the Role of Astrocytes
The Origin of Astrocyte Loss in AN
Potential Functional Consequences of Astrocyte Loss
Astroglia as Targets for Gonadal Steroid Hormones
Inflammation in AN and the Role of Astrocytes
Inflammation in AN
Astrocytes and Inflammation in the CNS
Astrocytes and Metabolic Diseases
The Hungry Astrocyte In Vitro
Astrocytes in Animal Models of AN
Gut Microbiota Alterations in AN and the Influence on Astrocytes
The Microbiome: General
The Microbiome: Anorexia Nervosa Animal Model
The Microbiome: Astrocytes
Conclusion and Outlook
References
Part VI: Targeting Astrocytes in Therapeutic Management of Neuropsychiatric Disorders
Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants
Introduction
Serotonin Receptors in the Treatments of MDD
5-HT1 Receptors
5-HT2 Receptors
Other Serotonin Receptors
Astrocytes as a Target for Classic Antidepressants
SSRIs
SNRIs
TCAs and MAOIs
Astrocytes in Treatments of Bipolar Disorders
Conclusion
References
Ketamine Action on Astrocytes Provides New Insights into Rapid Antidepressant Mechanisms
Astrocytes and Mood Disorders
Impact of Antidepressants on Astrocytes
Ketamine: The Fastest Acting Antidepressant
Ketamine Increases Astrocyte cAMP and Alters Single Vesicle Interactions with the Plasmalemma
Ketamine Induces Cholesterol Redistribution in the Astrocyte Plasmalemma
Ketamine Attenuates Mobility of Vesicles Delivering Kir4.1
References
Epilogue
Index
