Neuroglia in Neurologic and Psychiatric Disorders, Part II

1st Edition, Volume 210 - March 28, 2025
Editors: Alexei Verkhratsky, Lotje D. De Witte, Eleonora Aronica, Elly M. Hol
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 1 0 2 - 2
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 1 0 3 - 9

Neuroglia in Neurologic and Psychiatric Disorders, Part II discusses glia relative to neurologic and psychiatric disorders, emphasizing cross-disease-glial cell dysfun… Read more

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Neuroglia in Neurologic and Psychiatric Disorders, Part II discusses glia relative to neurologic and psychiatric disorders, emphasizing cross-disease-glial cell dysfunctions. Driven by advances in genetics, transcriptomics, electrophysiologic and imaging techniques, as well as by the increase in knowledge on neuropathologic features and underlying disease mechanisms, this book bridges the gap between neuroglia basic science and neuroglia clinical research.

Neuroglia in Neurologic and Psychiatric Disorders, Part II
Cover image
Title page
Table of Contents
Series Page
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
Contributors
PART I: Glia in neurological disorders
Chapter 1 General pathophysiology of neuroglia
Abstract
Keywords
Neuroglia in Neuropathology: Historic Prelude
Principles of Pathophysiology of Neuroglia
Conclusions
References
Chapter 2 Neuroglia in neurodegeneration: Alzheimer, Parkinson, and Huntington disease
Abstract
Keywords
Introduction: The Rise of Neurodegenerative Diseases
Neuroglia in Alzheimer Disease
Brief overview of AD pathogenesis and clinical presentation
AD mouse models
Astrocytes in AD
Microglia in AD
Oligodendrocytes in AD
Neuroglia in PD
Brief overview of PD pathogenesis and clinical picture
PD animal models
Astrocytes in PD
Microglia in PD
Oligodendrocytes and myelin in PD
Neuroglia in Huntington Disease
Brief overview of HD pathogenesis and clinical picture
HD animal models
Astrocytes in HD
Microglia in HD
Oligodendrocytes and myelin in HD
Astrotaupathies
Conclusions
Conflict of interest
References
Chapter 3 Neuroglia in neurodegeneration: Amyotrophic lateral sclerosis and frontotemporal dementia
Abstract
Keywords
Introduction
Amyotrophic lateral sclerosis
Frontotemporal dementia
Animal Models of ALS and FTD
SOD1 rodent models of ALS
TDP-43 rodent models of ALS and FTD
Chromosome 9 open reading frame 72 (C9ORF72) mutant models of ALS and FTD
TBK1 mutant models of ALS and FTD
OPTN mutant models of ALS and FTD
Glial Involvement in ALS/FTD: In Human Evidence
Glial histopathology in ALS and FTD: Postmortem evidence
In vivo imaging of glia in ALS and FTD
The Role of Glia in ALS and FTD
Astrocytes in ALS and FTD
Microglia in ALS and FTD
Oligodendrocytes in ALS and FTD
Glia-immunity cross talk
Glial Biomarkers in CSF and Blood
Glial-Based Clinical Trials in ALS and FTD
Conclusions
References
Chapter 4 Neuroglia in epilepsy
Abstract
Keywords
Epilepsy
Glia
Astroglia
Astroglia and the BBB in epilepsy
Cellular and molecular changes to astroglia in epilepsy
Astroglial contribution to immune and inflammatory functions in the context of epilepsy
Microglia
Oligodendroglia
Demyelination and epilepsy
Cellular and molecular changes to oligodendroglia in epilepsy
Potential Glial Therapeutic Targets
References
Chapter 5 Neuroglia pathology in genetic and epigenetic disorders of the central nervous system
Abstract
Keywords
Introduction
MicroRNAs of Individual Glial Cells
Examples of Genetic/Metabolic Diseases in Which Glial Cells Are Altered
Agenesis of the corpus callosum
Alexander disease
Rett syndrome
Fragile-X syndrome
Aicardi-Goutières syndrome
Down syndrome
Fetal alcohol spectrum disorder
Other Neuropathological Features That Involve Glial Cells
Satellitosis
α-B-crystallin as a glial marker of epileptic foci
Loss of subpial granular glial layer of Brun
Fetal astrocytic synthesis of keratan sulfate to guide axonal projections and insulate fascicles
Conclusions
Disclosures
References
Chapter 6 Neuroglia in stroke
Abstract
Keywords
Historic Prelude: From Hippocratic Apoplexy to Stroke
Stroke: General Remarks
Loss of Ion, Water, and Metabolic Homeostasis in the Ischemic Core and Penumbra
Astrocytes in Stroke: Neuroprotection and Reactive Astrogliosis
Astrocytic protection of neurons
Astrocytic perilesional limitans border formation around fibrotic scar tissue
Neuroglia and Brain-Wide Poststroke Pathology
Oligodendrocytes and White Matter Stroke
Microglia in Stroke
Conclusions
References
Chapter 7 Unraveling the complexity of microglial responses in traumatic brain and spinal cord injury
Abstract
Keywords
Introduction
Origin and Function of Microglia
Microglia in the Injured CNS: Primed for Immune Dysfunction and Chronic Neuroinflammation
Identification of Novel Microglial Phenotypic States in CNS Injury States
Microglia as a Therapeutic Target in TBI
Could Microglial Elimination or Forced Turnover in the Injured Brain be Neuroprotective for TBI?
Understanding Microglia Responses in Large Animal Models of TBI
Microglia in Human TBI: What Is the Current Evidence of Their Phenotypic and Functional Roles?
The Therapeutic Potential of Targeting Microglia Responses in SCI
Conclusion
References
Chapter 8 Astrocytes and microglia in multiple sclerosis and neuromyelitis optica
Abstract
Keywords
Historic Prelude
Overview of Multiple Sclerosis and Neuromyelitis Optica
Overview of Neuroglia in the Context of MS and NMO
Microglia in Multiple Sclerosis
Microglial phenotypes
Microglia contribution to pathogenesis of multiple sclerosis
Astrocytes in Multiple Sclerosis
Cross Talk Between Astrocytes and Microglia
Neurodegeneration as a Feature of MS: Role for Neuroglia
Neuroglia as a Therapeutic Target in Multiple Sclerosis
Targeting microglia
Targeting astrocytes
Neuroglia in NMO
Microglia
Astrocytes
Interaction of microglia and astrocytes with immune cells
Interaction of microglia and astrocytes with brain resident cells
Neuroglia as a Therapeutic Target in NMO
Microglia
Astrocytes
Conclusions
References
Chapter 9 Neuroglia in autoimmune encephalitis
Abstract
Keywords
Introduction
Astrocytes
Autoimmune GFAP astrocytopathy
Oligodendrocytes
MOG ab-associated AE
Microglia
Conclusions and Future Perspectives
References
Chapter 10 Neuroglia in leukodystrophies
Abstract
Keywords
Introduction
Astroglial Leukodystrophies
Alexander disease
Vanishing white matter disease
Megalencephalic leukoencephalopathy with subcortical cysts
Aicardi–Goutières syndrome
Genetic Etiology, Molecular Pathogenesis, and Genotype–Phenotype Correlation
Oligodendroglial Leukodystrophies
Krabbe disease or globoid cell leukodystrophy
Adult-onset autosomal dominant leukodystrophy
Metachromatic leukodystrophy
Canavan disease
Pelizaeus–Merzbacher disease
Hypomyelination with atrophy of basal ganglia and cerebellum
Microglial Leukodystrophies
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy or Nasu–Hakola disease
Hereditary adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
Conclusions
Acknowledgment
References
Chapter 11 Reciprocal interactions between glioma and tissue-resident cells fueling tumor progression
Abstract
Keywords
TAM-Glioma Cell Interactions
Soluble Factors Mediating TAM-Glioma Cross Talk
Modulation of the extracellular matrix
Contributions of TAM-Glioma Interactions for Tumor Behavior
Neuron-Glioma Interactions
Neuronal activity promotes tumor growth while glioma cells affect local neuronal network activities
Synaptic influences on glioma cells
Glutamatergic signaling and glioma excitatory drive
GABAergic signaling and chloride regulation in gliomas
Concluding remarks
Acknowledgments
References
Chapter 12 Neuroglia in hepatic encephalopathy
Abstract
Keywords
Hepatic Encephalopathy: Basic Information
Types of HE
Causes
Symptoms
Experimental Models
Alzheimer II Astrocytes: The Response of Astrocytes to Chronic HE
Metabolic Remodeling of Astrocytes at the Onset of ALF
Astrocytic Impact on the Excitation/Inhibition Balance
Astrocytic contribution to alterations of glutamate and GABA synthesis in HE
Astrocytic interference with the glutamatergic/GABAergic neurotransmission balance at steps beyond neurotransmitter synthesis
Malfunctional Astrocyte and Impaired Ion Fluxes
Astrocyte Swelling and Brain Edema
Intracellular osmotic imbalance
The oxidative/nitrosative stress and mitochondrial dysfunction
Neurogliovascular unit and perivascular edema
The Asthenic Astrocyte
Neuroinflammation: A Consequence of Systemic Inflammation and Reactive Microgliosis
Concluding Remarks
Acknowledgments
References
Chapter 13 Neuroglial responses to bacterial, viral, and fungal neuroinfections
Abstract
Keywords
Neuroinfections and the Nervous System
Neuroinvasiveness, Neurotropism, and Neurovirulence of Pathogens: An Overview
Neuroglial Roles in Bacterial Infections: A Spotlight on Meningoencephalitis-Causing E. coli K1
Bacterial CNS infection
Microglia and astrocytes in meningoencephalitis-causing E. coli K1 infection
Microglial Roles in Viral Infections
Non-neurotropic viral infection and the CNS
Toll-like receptors and IFN type 1-mediated response
Purinergic signaling as a driver of microglial chemotaxis in viral infection immune response
Glial Roles in Fungal Infections
Microglia and astrocytes in neuroinvasive C. neoformans infection
Neuroglia in SARS-COV-2 and COVID-19: A Spotlight
SARS-CoV-2 pathway to the brain
Neurodegenerative susceptibility following SARS-CoV-2 infection
Macrophages and Microglia as Viral Reservoirs in HIV: A Spotlight
Neuroglia as Pharmacologic Targets During Neuroinvasive Infections
Neuroglia as therapeutic target in HIV
Neuroglia as therapeutic targets in nematode infection
Bacterial CNS infection: Therapeutic insight
Concluding Remarks
References
Chapter 14 Physiology and pathophysiology of the retinal neuroglia
Abstract
Keywords
The Retina and the Visual System
Cellular Organization of the Retina
Retinal Astroglia: Müller Cells and Astrocytes
Astroglia: General remarks
Müller cells: The morpho-functional integrators of the retina
Müller glia: Numbers and morphology
Physiology of Müller glia
Functions of Müller glia
Retinal astrocytes
Oligodendroglia of the Retina
Microglia of the Retina
Pathophysiology of Retinal Neuroglia
Macular telangiectasia type 2
Glaucoma
Age-related macular degeneration
Retinitis pigmentosa
Diabetic retinopathy
Retinopathy of prematurity
Endophthalmitis
Conclusions
Acknowledgments
References
Chapter 15 From womb to world: The interplay between maternal immune activation, neuroglia, and neurodevelopment
Abstract
Keywords
The Dynamic Role of Neuroglia in Brain Development and Adulthood
Maternal Immune Activation
Inflammation and Cytokines Associated With MIA
Temporal Stage of Infection and Cytokine Exposure
Modeling MIA: Animal and Human
Influenza A-mediated MIA model
The poly(I:C)-mediated MIA model
Lipopolysaccharide (LPS)-mediated MIA model
Human-induced pluripotent stem cell (iPSC) technology
Double-hit MIA models
Maternal Immune Activation Effect on Neuroglia
MIA and astroglia
MIA and oligodendroglia
MIA and microglia
The COVID-19 Pandemic
Conclusions, Speculations, and Future Directions
References
Part II: Neuroglia in psychiatric disorders
Chapter 16 Neuroglia in mood disorders
Abstract
Keywords
Introduction
Mood Disorders
Total Glia
Imaging
Animal models
Human postmortem
Biomarkers in blood and CSF
Summary
Astrocytes
Imaging
Animal models
Human postmortem
Biomarkers in blood and CSF
Neurotrophic factors
Other astrocytic markers
Summary
Oligodendrocytes
Imaging
Animal models
Human postmortem
Biomarkers in blood and CSF
Summary
Microglia
Imaging
Animal models
Human postmortem
Biomarkers
Other microglia specific markers
Summary
Mood Disorder Treatments
Antidepressants
Lithium
Deficiencies in Glia–Glia Crosstalk and Mood Disorders
Conclusions and Future Directions
References
Chapter 17 Neuroglia in autism spectrum disorders
Abstract
Keywords
ASD Diagnosis and Symptoms
Genetic Factors Associated With ASD
Prenatal Inflammation Is a Risk Factor for ASD
The Role of Neuroglia in ASD-Associated Changes in Neurons
Myelin Alterations Underlying Brain Connectivity
References
Chapter 18 Neuroglia in eating disorders (obesity, Prader-Willi syndrome and anorexia nervosa)
Abstract
Keywords
Introduction
Homeostatic and Non-homeostatic Control of Feeding Behavior
Obesity
Tanycytes
Microglia
Astrocytes
Oligodendrocytes
Prader-Willi Syndrome
Microglia and astrocytes
Oligodendrocytes
Anorexia Nervosa
Microglia
Astrocytes
Conclusion
References
Chapter 19 Neuroglia in Tourette syndrome and obsessive-compulsive disorder
Abstract
Keywords
Gilles de la Tourette's Syndrome
Microglia dysfunction in TS
Are astrocytes involved in TS?
Oligodendroglia, myelin and TS
Obsessive-Compulsive Disorder
OCD as a microgliopathy
Astrocytes, glutamate, and pathologic grooming
Oligodendroglia and myelination in OCD
The Particular Case of PANDAS/PANS
Final Notes
References
Chapter 20 Neuroglia in anxiety disorders
Abstract
Keywords
Introduction
Overview of Neuroglia
Preclinical Animal Models of Stress and Anxiety
Overview of Specific Brain Regions Involved in PTSD
Microglia
Microglia and epigenetics
Microglia and the neuroimmune system
Oligodendrocytes
Oligodendrocytes in preclinical models
Oligodendrocytes in clinical PTSD
Astrocytes
Astroglia in clinical PTSD
Astroglia in neuroimmune response
Pharmacologic Treatments for PTSD
Future Steps for Understanding Neurobiology of Anxiety
Conclusion
Acknowledgments
References
Chapter 21 Neuroglia in substance use disorders
Abstract
Keywords
Introduction
Neuroglia
Neuroglial Mechanisms Underlying Substance Use
Opioids
Opioid use disorder treatments
Stimulants
Stimulant use disorder treatments
Alcohol
Alcohol use disorder treatments
Nicotine
Nicotine use treatments
Cannabis
Cannabis use treatments
Gut Microbiome
Gut microbiome and neuroglia
Conclusions
References
Chapter 22 Neuroglia in suicide
Abstract
Keywords
Risk Factors and Treatments for Suicide
Neuroglia Biology Provides Molecular Features of Suicide
Astroglia in suicide
Microglia in suicide
Oligodendroglia in suicide
Pitfalls in Suicide Research
Animal models of suicide
Human postmortem brain samples in suicide studies
Novel Neuroglial Changes in Suicide
Suicide and psychiatric disorders: Commonalities and differences in neuroglia
Neuroglia changes in suicide can be similar in different psychiatric disorders
Psychiatric suicides and nonpsychiatric suicides may have shared or independent neuroglia changes
Microglia are involved in resilience to suicide
Neuroglia and Antisuicidal Therapies
Conclusions
References
Index

Alexei Verkhratsky

Professor Alexei Verkhratsky, PhD, DSc, is an internationally recognised scholar in the field of cellular neurophysiology, best known for his contributions to our knowledge of the physiology and pathophysiology of neuroglia. He started glial research in 1989 in Heidelberg in the laboratory of Helmut Kettenmann. In a series of highly cited conceptual papers, he outlined basic principles of glial physiology and pathophysiology, which significantly influenced this rapidly developing area of neuroscience.

Affiliations and expertise

University of Manchester, Manchester, UK

Lotje D. De Witte

Dr. de Witte is a psychiatrist with a background in preclinical research in the fields of virology and immunology. She is an MD PhD interested in how the immune system plays a role in psychotic disorders. In parallel to her residencies in psychiatry, she started her own research group at the Brain Center Rudolf Magnus in Utrecht, the Netherlands investigating the prevalence and role of neuronal auto-antibodies and neurotropic pathogens in psychotic disorders. He research has resulted in a novel and distinctive research line studying the phenotype and function of microglia in psychotic disorders.

Affiliations and expertise

Psychiatrist, Icahn School of Medicine at Mount Sinai. New York, USA

Eleonora Aronica

Prof. E.M.A. Aronica is professor of Neuropathology at the University of Amsterdam’s Faculty of Medicine (AMC-UvA). Her research focuses on understanding the pathogenesis, epileptogenesis and pharmacoresistance of focal chronic pharmacoresistant epilepsy, as well as featuring translational aspects. The aim is to find an effective treatment for patients with epilepsy by mapping biological and molecular signalling pathways that contribute towards the development and progression of epilepsy and associated comorbidity. Aronica studies the control mechanisms of inflammatory processes, microRNAs, biomarkers to predict and diagnose the development of disease. Aronica focuses on neuropathological and applied research for patients with neurological diseases. She has published more than 300 peer-reviewed articles and several chapters for books.

Affiliations and expertise

Neuropathologist, Department of (Neuro) Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands

Elly M. Hol

Elly Hol is professor of “Glia biology of brain diseases” at the Utrecht University and professor of "Biology of glia and neural stem cells” at the University of Amsterdam. Her research is focused on the role of glial cells in brain diseases, including Alzheimer’s disease, stroke, schizophrenia and glioma. The overall aim is to elucidate the molecular and functional changes in glia that contribute to the pathogenesis of neurological and psychiatric diseases. Her work is translational and includes studies on glial cells in human post-mortem brain tissue, in human cell models, and in mouse models for brain diseases. She is a member of Academia Europaea, member of the editorial board of Glia, chair of the scientific advisory board of Alzheimer Nederland, chair of GliaNed, director of the Neuroscience Master and PhD program of the Utrecht University Graduate School of Life Sciences, and director of education for the Division Brain at the UMCU.

Affiliations and expertise

Neuroscientist, Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands

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Neuroglia in Neurologic and Psychiatric Disorders, Part II

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Innovate. Sustain. Transform.

Institutional subscription on ScienceDirect

Alexei Verkhratsky

Lotje D. De Witte

Eleonora Aronica

Elly M. Hol

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