The Biology of Glial Cells: Recent Advances

Description

This book reviews the role of glial cells (astrocytes, microglia, oligodendroglia, satellite cells, and Schwann cells) in neuronal health and diseases. It discusses the latest advances in understanding their origin, differentiation, and hemostasis. The book also examines the role of microglial cells in central nervous system (CNS) development, maintenance, and synaptic plasticity. Further, the book presents the functions of astrocytes in healthy CNS and their critical role in CNS disorders, including Parkinson's and Alzheimer's diseases. Notably, the book describes the pathobiology, molecular pathogenesis, stem cells, and imaging characteristics of gliomas. It defines the role of glial cells in regulating iron homeostasis and their effect on the neurodegeneration of neurons. Lastly, it covers the structure, function, and pathology of oligodendrocytes and their role in neuronal health and disease. Foreword Preface About the Book Contents About the Editors Abbreviations Glial Biology: A Historical Perspective 1 Introduction 1.1 Astrocytes 1.2 Oligodendrocytes 1.3 Microglia 2 Biology of Glia: Part I-Astrocytes 2.1 History 2.2 Morphology 2.3 Functions Astrocyte Excitability Astrocyte-Neuron Interaction Astrocytes and Synapses 2.4 Astrocytes and Neurovascular Regulation 2.5 Astrocytes and Brain Energy Metabolism 2.6 Astrocytes and Non-Neural Cells: Glia-Glia Interaction 2.7 Astrocytes and Neuroinflammation 2.8 Astrocytes and Other Neuropathological Conditions 3 Biology of Glia: Part II-Microglia 3.1 History 3.2 Morphology 3.3 Distribution 3.4 Functions Microglia in Immune Regulation Role of Microglia in Neuroinflammation and Diverse Neuropathologies 4 Biology of Glia: Part III-Oligodendrocytes 4.1 History 4.2 Origin and Development of Oligodendrocytes 4.3 Oligodendrocytes and Myelination 4.4 Non-Myelinating Functions of Oligodendrocytes and OPCs 4.5 Oligodendrocytes and CNS Pathology References Basic Biology of Astrocytes 1 Introduction 1.1 History 1.2 Classification 2 Embryogenesis and Development of CNS 2.1 Development of Glial Cells 2.2 Synaptogenesis and Synapse Maintenance 3 Markers and Functions 3.1 Cell-Specific Markers Astrocytes 3.2 Functions Role of Astrocytes in Blood-Brain Barrier (BBB) Role of Astrocytes in Brain Functions Role of Astrocytes in Neuronal Functions and Communication 4 General Pathophysiology of Astrocytes 4.1 Reactive Astrogliosis 5 Conclusion References Oligodendrocyte: Structure, Function and Pathology 1 Oligodendrocytes 1.1 Myelination 1.2 Structure and Composition of Myelin Defects in Myelination and Neuropathologies Primary Demyelinating Diseases Multiple Sclerosis Secondary Demyelinating Diseases Acute Disseminated Encephalomyelitis (ADEM) Neuromyelitis Optica (NMO)/Neuromyelitis Optica Spectrum Disorder (NMOSD) Leukodystrophies Demyelination Due to Mutations and Defects in Oligodendrocyte- and Myelin-Related Genes Mutations in Microglial and Astrocytic Genes and Leukodystrophies Viral Encephalopathies Vascular (Hypoxia/Ischaemia) Metabolic/Nutritional Other Concerns for Demyelination Remyelination Strategies References Oligodendroglial-Astroglial Cell-Cell Communication in the Central Nervous System 1 Introduction 2 The Myelin Sheath 3 Panglial Astro-Oligo Metabolic Coupling and Maintenance of CNS Homeostasis 4 Glial Biology in Neurodegeneration and Demyelination 5 The Biology of Gap Junctions 6 Properties of Gap Junctions: Synthesis, Oligomerization, Trafficking, and Degradation 7 Functional Importance of Astrocytic and Oligodendrocytic Gap Junctions 8 Conclusion 8.1 Gap Junctions as a Novel Target in Demyelinating Diseases References Oligodendroglial Gap Junction Communication in CNS Myelination and Demyelination 1 Gap Junctions in the Nervous System 2 Gap Junction Protein Mutations in Health and Disease 3 The Cx43/Cx47 Axis in CNS Myelination 4 Gap Junctions in Human CNS Demyelinating Disease Multiple Sclerosis 5 Remodeling of Gap Junction Proteins in Experimental Animal Models of Multiple Sclerosis 6 Alteration of Cx43/Cx47 Axis in Respect to Viral Model of Multiple Sclerosis References Generation and Maturation of Macroglia in the Central Nervous System 1 Introduction 2 Astrocytogenesis 3 Differentiation and Specification of Astrocytes 4 Morphological and Functional Maturation of Astrocytes 4.1 Astrocyte Markers 5 Genesis of Oligodendroglia 6 Specification of Oligodendrocyte Precursors (OPCs) 7 Oligodendrocyte Differentiation 8 OPCs´ Migration, Maturation and Myelination References Origin and Development of Microglia 1 Introduction 2 Origin of Microglia 3 Early Specification and Differentiation of Microglia 3.1 Transcription Factors Required for Microglia Development and Homeostasis 3.2 Extrinsic Factors Required for Microglia Development and Homeostasis 4 Colonization, Distribution, and Terminal Differentiation of Microglia in Developing Brain Parenchyma 5 Microglial Markers to Study Their Phenotype, Distribution, and Functions 6 Perturbations in Microglial Development and Consequences 7 Perspectives References Biology of Astrocytes in CNS Infection 1 Introduction 2 Reactive Astrogliosis 3 Subtypes of Astrocytes 4 A1 Subtype 5 A2 Subtype 6 Pathobiology of Astrocytes in Various CNS Infections 6.1 Viral Infections (Figs. 1, 2, 3, 4, 5, and 6) Herpesvirus Infections Flavivirus Infections Human Immunodeficiency Virus (HIV) Progressive Multifocal Leukoencephalopathy (PML) 6.2 Bacterial Infections (Figs. 7 and 8) Bacterial Meningitis Tubercular Meningitis (TBM) 6.3 Fungal Infections (Figs. 9 and 10) Cryptococcal Meningoencephalitis Aspergillosis 6.4 Parasitic Infections (Figs. 11, 12, and 13) Toxoplasma Encephalitis Cerebral Malaria (CM) Neurocysticercosis (NCC) 7 Conclusion References Role of Reactive Astrocytes in Alzheimer´s Disease 1 Introduction 2 Astrocytes in AD 2.1 Types and Subtypes Physiological Subtypes Astrogliopathology Astrocyte Reactivity or Reactive Astrogliosis Astroglial Atrophy 2.2 Metabolic Balance and Imbalance Regulated by Astrocytes in AD Metabolic Dysregulation in AD Dysregulation in Astrocytic Metabolic Enzyme Activity Altered Insulin Metabolism 2.3 Reactive Astrocytes in Neuroinflammation in AD Importance of Neuroinflammation in AD Astrocytes Taking a Center Stage Blood-Brain Barrier in AD Microglia-Astrocyte Cross Talk Astrocytic Neuroinflammatory Profile Correlates with AD Stage 2.4 Role of Astrocytes in Abeta Clearance and Production Abeta Uptake and Clearance Abeta Production and Astrocytes A Hypothesis for Astrocyte Function in Abeta Clearance or Its Production 2.5 Reactive Astrocytes in Tau Pathology 2.6 Role of Astrocytes in Modulating Synaptic Plasticity in AD Physiological Role in Synaptic Health Reactive Astrocytes in Synaptic Dysfunction in AD 2.7 Role of Astrocytes in Neurotransmitter Recycling in AD Astrocytes in Glutamate Regulation in AD Astrocytes in GABA Regulation in AD 2.8 Role of Astrocytes in Neuron Death and Survival in AD Reactive Astrocytes Mediating Neuron Death Reactive Astrocytes in Neuron Survival 2.9 Astrocytic Biomarkers in AD Patients 2.10 Astrocytes as Targets for Therapy in AD Astrocyte Subtype-Based Therapy Neuroinflammatory Cytokines as Therapeutic Targets Targeting Metabolic Dysfunctions for Therapy Aquaporin as a Therapeutic Target 3 Conclusions References Role of Astrocyte Dysfunction in Parkinson´s Disease Pathogenesis 1 Introduction 2 Astrocytes: Role as Forming the Niche for DA Neurons 3 Astrocytes and Their Heterogeneity and Region Specificity 4 PD-Related Genes Associated with Astrocytes (PARK-7, SNCA, LRRK2, PARK-2, PLA2G6, ATP13A2, GBA, PINK1) 5 Deleterious Astrocytic Changes in PD 6 Neuroprotective Role of Astrocytes in PD 7 Cell-Based Treatment Strategy to Target Astrocyte Regeneration and Replacement 8 Conclusions References Astroglial Pathology in Major Depressive Disorders: Metabolic and Molecular Aspects 1 Introduction 1.1 Major Depressive Disorders 2 Glial Contributions to Neural Functions 2.1 Astrocytes as an Integral Part of the Neurovascular Unit and Synapse 2.2 Astrocytes Contribute to Synapse Formation and Refinement 2.3 Astrocytes are Important Players in Neurological Disorders 3 Techniques to Study Energy Requirement for Neural Function 3.1 Positron Emission Tomography (PET) 3.2 13C Nuclear Magnetic Resonance Measurement of Neurometabolic Activity Measurement of Astroglial Activity 4 Brain Energy Metabolism 4.1 Metabolic Activity of Neurons 4.2 Neurotransmitter Cycling 5 Neuronal Metabolic Activity in Depression 6 Neuron-Glia Communication in Depression 7 Glial Pathology in Major Depressive Disorder 7.1 Astrocytic Pathology in MDD Immunohistochemical Findings Studies Involving mRNA and Protein Level 7.2 Oligodendrocyte Pathology in MDD 7.3 Neuroinflammation in Major Depressive Disorder Dysfunction in Hypothalamus-Pituitary-Adrenal (HPA) Axis Dysfunction in Kynurenine Pathway Microglial Activation 8 Manipulation of Glial Function as a Therapeutic Strategy for Neuropsychiatric Disorders 8.1 Classical Antidepressants Modulate Astrocytic Activity 8.2 Atypical and Fast-Acting Antidepressants Modulate Astrocytic Activity 8.3 Epigenetic-Based Potential Antidepressive Molecules 8.4 Genetic Manipulation of Astrocytes 8.5 Exercise Modulates Astrocytic Function in Depressive Disorders 8.6 Optogenetic-Based Modulation of Astrocytic Functions 9 Limitations 10 Conclusion References Glia in Epilepsy: An Overview 1 Brief Introduction to Epilepsy 2 Reactive Gliosis in Epileptic Foci 3 Water and K+ Buffering 4 Glutamate Release and Metabolism 5 Gliotransmission: Role of Ca2+ Signaling 6 Cell-Cell Communication: Role of Gap Junctions 7 Vasculature and the BBB in Epilepsy 8 Glia-Mediated Neuroinflammation 9 Future Perspectives References Tumors of the Glia: Recent Advances 1 Introduction 2 Adult-Type Diffuse Gliomas 2.1 WHO 2021 Classification of Adult-Type Diffuse Gliomas 2.2 Clinical-Pathological Characteristics of Adult-Type Diffuse Gliomas Astrocytoma Astrocytoma, IDH-Mutant, WHO Grade 2 Astrocytoma, IDH-Mutant, WHO Grade 3 Astrocytoma, IDH-Mutant, WHO Grade 4 Oligodendroglioma (ODG) Oligodendroglioma, IDH-Mutant, and 1p/19q Co-deleted, WHO Grade 2 Oligodendroglioma, IDH-Mutant, and 1p/19q Co-deleted, WHO Grade 3 Glioblastoma (GB) Essential Diagnostic Criteria for Glioblastoma, IDH-Wild Type (Louis et al. 2021a) Oligoastrocytic Gliomas 2.3 Key Molecular Alterations in Adult-Type Diffuse Gliomas (Table 1) Mutations of Isocitrate Dehydrogenase 1 and 2 (IDH1/2) Genes Co-deletion of Chromosomes 1p and 19q Mutation of Alpha Thalassaemia Mental Retardation, X Linked (ATRX) Gene Mutation of TP53 Gene Amplification of Epidermal Growth Factor Receptor (EGFR) Gene Mutation in the Promoter Region of Telomerase Reverse Transcriptase (TERT) Gene Homozygous Deletion of Cyclin-Dependent Kinase Inhibitor 2A/2B (CDKN2A/2B) Gene Promoter Methylation of O6-Methylguanine-DNA Methyltransferase (MGMT) Gene 3 Pediatric-Type Diffuse Gliomas 3.1 WHO 2021 Classification of Pediatric-Type Diffuse Gliomas 3.2 Pediatric-Type Diffuse Low-Grade Gliomas (PLGG) Key Molecular Alterations in PLGG KIAA1549-BRAF Fusions BRAF V600E Mutation 3.3 Pediatric-Type Diffuse High-Grade Gliomas (PHGGs) Key Molecular Alterations in PHGG H3K27M Mutation H3G34 Mutation 4 Circumscribed Gliomas 4.1 WHO 2021 Classification of Circumscribed Gliomas 4.2 Pilocytic Astrocytoma 4.3 Pleomorphic Xanthoastrocytoma 4.4 Subependymal Giant Cell Astrocytoma 5 Conclusion Annexure I: Contributions from Neuropathology Unit, Department of Pathology, AIIMS, New Delhi References Astroglial Iron Homeostasis and Neurodegenerative Diseases 1 Introduction 2 Role of Astrocytes in Maintenance of Neurons 3 Iron Is an Essential Component for Neuronal Function 4 Iron Homeostasis in Astroglia 5 Role of Astrocytes in Neuronal Iron Homeostasis 6 Dysregulation of Iron Homeostasis During Neurodegeneration: Correlation with Astrocyte Function 7 Future Perspectives References Glial Cells as Key Orchestrators of Neural Degeneration in Basal Ganglia Disorders 1 Introduction 2 Morphometric Studies of Glia in Normal Human Striatum 3 Significance of Glia in Developing Basal Ganglia 3.1 Astroglia and Ageing Basal Ganglia 3.2 Limited Focus on Oligodendroglia 3.3 Microglia in Basal Ganglia 4 Neurotoxins in Understanding Disease Pathogenesis 4.1 Ibotenic Acid-Induced Lesions 4.2 6-Hydroxydopamine-Induced Striatal Damage 4.3 MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine) Induced PD 5 Elemental Metals 6 Glia and Growth Factors 7 Role of Glia in Cell Therapy 8 Alpha-Synuclein 9 Select Diseases of the Basal Ganglia 9.1 Parkinson´s Disease 9.2 Multiple System Atrophy (MSA) Astrocytes and Microglia in MSA Disease and Symptoms Overlap Animal Models of MSA 9.3 Cortico-Basal Degeneration Vis-à-vis Progressive Supranuclear Palsy 9.4 Wilson´s Disease 9.5 Other Basal Ganglia Disorders References Interplay Between Microglia and Astrocytes During Neuroinflammation: Lessons Learnt from In Vitro and In Vivo Models of Sporad... 1 Introduction 2 Lessons from the Model of sALS 3 Circulating Pathology: Does CSF Hold Clues? 4 Neuroinflammation in sALS 4.1 Astrocytes 4.2 Microglia 5 Chitotriosidase as the Neuroinflammatory Marker in ALS 6 Conclusion References Microglia Orchestrate Inflammation via HSP60-Driven Signalling Pathway: A Road Map of Molecular Mechanism 1 Introduction 2 Classification of Heat Shock Proteins (HSPs) 3 Cellular Functions of HSPs 3.1 Chaperone Activity 3.2 Modulators of Apoptosis 3.3 Interaction with Cytoskeletal Proteins 3.4 Regulatory Role in Neurodevelopment 4 Role of HSPs in Health and Disease 4.1 Neuroprotection 4.2 Cancer 4.3 Diabetes 5 HSP60: Warrior in Neuroinflammatory Battles 6 Structure of HSP60 7 Many Faces of HSP60: In Context of Pathological Conditions 7.1 Role in Bacterial Infection 7.2 Role in Viral Infections 7.3 Role as a Pathogenic Protein 7.4 Role in Neurodegenerative Disorders 7.5 Role as an Immunomodulator 8 Microglia and HSP60: Partners in Crime 8.1 Role of Microglia in Neuroinflammation Role of IL-1β in Microglial Activation Administration of IL-1β Causes Microglial Activation Inducing Inflammation Both In Vitro and In Vivo Proteomic Profiling Depicts Increased Expression of HSP60 Post-IL-1β Treatment of Microglial Cells IL-1β Administration Leads to Increased Expression of HSP60 Both In Vivo and In Vitro and Aids Its Secretion into Extracellula... Pattern Recognition Receptors in Microglia Role of TLR4 in HSP60-Induced Inflammation Toll-Like Receptors and Their Structure 8.2 HSP60 Plays a Crucial Role in IL-1β-Mediated NF-κB Phosphorylation and Its Nuclear Localization 8.3 HSP60 Regulates Endogenous IL-1β Production in Activated Microglia by Stimulating NLRP3 Inflammasome Pathway NLRP3 Inflammasome: Molecular Complex Regulating Caspase Activation Structure of NLRP3 Inflammasome 8.4 HSP60 Causes Mitochondrial Damage and Accelerates Production of Reactive Oxygen Species HSP60 Plays a Key Role in IL-1β-Induced Caspase-1 Activation 8.5 HSP60 as a Mediator of Endogenous IL-1β Production in Activated Microglia 8.6 Evaluating HSP60´s Contribution in Inducing Microglial Activation and Inflammation 8.7 HSP60 Aggravates IL-1β-Induced Microglial Activation and Leads to Inflammation by Phosphorylating Mitogen-Activated Protei... ERK Pathway JNK Pathway p38 MAPK Pathway 8.8 HSP60-Induced Microglial Activation and Subsequent Inflammation Are Dependent on p38 MAPK Pathway 9 Microglia and Japanese Encephalitis Virus: Molecular Interdependence of HSP60 and NLRP3 in Regulating Inflammation Pathways 9.1 Introduction to Japanese Encephalitis Virus 9.2 Microglia Act as Companion in JEV-Driven Neuroinflammation 9.3 Japanese Encephalitis Virus Evokes Activation of NLRP3 Inflammasome 9.4 HSP60 Bridges JEV-Induced IL-1β Production in Microglia 9.5 Abrogation of HSP60 Amends Inflammatory Cascade 10 Summary References Biphasic Role of Microglia in Healthy and Diseased Brain 1 Introduction 2 The Canonical Bipolar M1/M2 State 3 Heterogeneity of Microglia 4 Microglia in Neuropsychiatric Disorders 4.1 Major Depressive Disorder (MDD) 4.2 Depression and Anxiety 4.3 Bipolar Disorder 4.4 Schizophrenia 5 Microglia in Neurodegenerative Diseases 6 Alzheimer´s Disease 7 Parkinson´s Disease 8 Huntington´s Disease 9 Amyotrophic Lateral Sclerosis 10 Multiple Sclerosis 11 Clinical Significance 12 Conclusions References Multidimensional Roles of Microglial Cells in Neuroviral Infections 1 Introduction 2 Role of Microglial Cells During Neuroviral Infections 2.1 Antiviral Roles of Microglial Cells During Neuroviral Infections 2.2 Pro-Inflammatory Response of Microglial Cells During Neuroviral Infection 2.3 Microglial Cells Affect Adaptive Immune Response During Neuroviral Infection 3 Microglia Perturb Cell Death Pathways During Viral Infection 4 Other Roles of Microglia During Viral Infection 4.1 Microglial Activation During Virus-Induced Amyloid-beta Plaque Formation 4.2 Roles of Microglial Purinergic Receptors During Viral Infection 4.3 Necroptosis and Microglia 5 Conclusion References Microglia Aging 1 Introduction 2 Microglial Aging and Brain Health 3 Aging of Microglia 4 Aging and Microglial Heterogeneity 5 Neuroinflammation in the Aging Brain 6 Priming of Microglia 7 Lipofuscin in Aging Microglia 8 ROS and Aging Microglia 9 Aging and Immunoinhibitory Signaling 10 Phagocytosis in Aging Brain 11 Microglial Functional Phenotyping with Aging 12 Counteracting Aging of Microglia 13 Microglia Repopulation in the Aging Brain 14 Modeling Aging Microglia 15 Conclusion References The Emerging Role of Satellite and Schwann Cells of the Peripheral Neuroglial System in Nerve Repair 1 Introduction 2 Myelinating and Nonmyelinating Schwann Cells 3 Schwann Cells, Nerve Injury, and Repair 4 Neuroinflammation, Schwann Cells, and Satellite Glial Cells 5 Schwann Cells in Spinal Cord Injury and Repair 6 Satellite Glial Cells in Nerve Repair and Pain 7 Conclusion References Insights in the Role of Glia in Mediating Brain Plasticity in Health and Disease 1 Glia, Neuroinflammation, and Neuronal Plasticity 1.1 Role of Astrocytes in Synaptic Plasticity 1.2 Role of Microglia in Synaptic Plasticity 1.3 Underlying Role of Glia in Synaptic Dysfunction in Neuropsychiatric Disorders Major Depressive Disorder Schizophrenia Bipolar Disorder 1.4 Studies from our Lab Exploring the Link Between Neuroinflammation and Synaptic Plasticity 1.5 Remarks 2 Glia and Microglia in Brain Injury 2.1 Astrocytes Following CNS Injury 2.2 Astrocytic Subtypes in the Injury Response 2.3 Gaps in the Knowledge 2.4 Microglia Following CNS Injury 2.5 Microglial Subtypes in the Injury Response 2.6 Gaps in the Knowledge 2.7 Remarks References The Glial Perspective of Energy Homeostasis, Neuroinflammation, and Neuro-nutraceuticals 1 Introduction 2 Glial Cells in Energy Homeostasis 2.1 The Warden Astrocytes 2.2 Tanycytes as Gatekeepers of CNS 2.3 The Warrior Microglia 3 Therapeutic Potential of Naturally Occurring Immunomodulators 3.1 Curcumin 3.2 Blueberries 3.3 Withania somnifera 3.4 Tinospora cordifolia 3.5 Bacopa monnieri 3.6 Ganoderma lucidum 3.7 Allium sativum 3.8 Spirulina 4 Concluding Remarks References The Role of Glia in Huntington´s Disease 1 Introduction 2 Microglial Activation and Reactive Astrogliosis: Key Processes in Neuroinflammation 3 Neuroinflammation in HD 4 Therapeutics Targeting Neuroinflammatory Components 5 Conclusions References Endogenous Mediators of Neuroinflammation: The Endocannabinoid System at the Retina 1 Introduction 2 Endocannabinoids as Immunomodulators in the CNS 3 Endocannabinoids in Ocular Diseases 4 Endocannabinoid System in the Retina 5 Modulation of Muller Glia Immune Response by Endocannabinoids and Its Implications in Glial Physiological Functions 6 Inflammation and Changes in Endocannabinoid System Genes in Muller Glia 7 Conclusion References Drosophila melanogaster: An Immaculate Model for Glial Research 1 Introduction 2 Drosophila: A Prime Model for Glia Research 3 Gliogenesis in Drosophila 3.1 Different Glial Lineages in Drosophila 3.2 Establishment of Glial Cell Fate 4 Drosophila Glial Subtypes and Their Morphology 4.1 Midline Glia 4.2 Surface Glia Perineurial Glia Subperineurial Glia 4.3 Cortex Glia 4.4 Neuropil-Associated Glia Astrocyte-Like Glia Ensheathing Glia Wrapping Glia 5 Anatomical Comparison of Mammalian and Drosophila Glial Subtypes 6 The Role of Glia in Neurodegeneration 6.1 Mechanism of Glial Pathogenesis in Neurodegeneration: Answers from Fly Models Amyotrophic Lateral Sclerosis Parkinson´s Disease Alzheimer´s Disease Frontotemporal Dementia/Non-AD Dementia Polyglutamine Diseases 7 Concluding Remarks References In Vitro Models of Astrocytes: An Overview 1 Introduction 2 Models for Primary Cell Cultures 3 Differentiation of Progenitor Cells for In Vitro Cultures 4 In Vitro Models for Astrocyte Monoculture 5 In Vitro Models for Astrocyte-Neuron Interactions 6 In Vitro Models for Communication of Astrocyte-Brain Microvascular Endothelial Cells 7 Induced Pluripotent Cell (iPSC) Models of Astrocyte Cultures 8 3D Models Used for Astrocytes 9 Conclusion References Index