Neuroglia in the Healthy Nervous System, Part I

1st Edition, Volume 209 - March 22, 2025
Imprint: Elsevier
Editors: Elly M. Hol, Lotje D. De Witte, Eleonora Aronica, Alexei Verkhratsky
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 1 0 4 - 6
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 1 0 5 - 3

Neuroglia in the Healthy Nervous System, Part I provides insights into newly emerging developments in neuroglia biology, focusing on the healthy nervous system. Driven by advanc… Read more

Purchase options

World Book Day Celebration!

Save up to 30% on books and eBooks!

Shop now

Institutional subscription on ScienceDirect

Request a sales quote

Neuroglia in the Healthy Nervous System, Part I provides insights into newly emerging developments in neuroglia biology, focusing on the healthy nervous system. Driven by advances in genetics, transcriptomics, electrophysiological, and imaging techniques, this volume bridges the gap between neuroglia basic science and neuroglia clinical research. The book provides an overview of neuroglia biology, highlighting emerging technologies used to unravel the role of neuroglial cells in specific brain functions. The book also discusses strategies using neuroglia as a therapeutic target.

Neuroglia in the Healthy Nervous System, Part I
Cover image
Title page
Table of Contents
Series Page
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
Contributors
Chapter 1 Neuroglia in the healthy brain
Abstract
Keywords
Neuroglia: Definition and Classification
References
Chapter 2 Evolution of neuroglia: From worm to man
Abstract
Keywords
Evolution of the Nervous System
Neuroglia: Homeostatic and Defensive Arm of the Nervous System
Evolution of Neuroglia: General Remarks
Neuroglia in Invertebrates
General remarks
Cnidaria and Ctenophora—Do they contain ancient forms of supportive cells in the nervous system?
Platyhelminthes
Nematoda
Tardigrade
Annelida
Insects
Mollusca
Neuroglia in Vertebrates
Echinodermata
Amphioxus
Elasmobranchii
Teleosts
Amphibians
Sauropsida
Mammals
Evolution of Astrocytes Form High Primates to Humans
Protoplasmic astrocytes
Fibrous astrocytes
Interlaminar astrocytes
Varicose projection astrocytes
Quest toward the identification of genes that underlie astrocyte evolution
Evolution of Oligodendroglia and Myelin
Evolution of Microglia
Conclusions: Animal Models for Glial Research From the Evolutionary Perspective
References
Chapter 3 Orchestrating the neuroglial compartment: Ontogeny and developmental interaction of astrocytes, oligodendrocytes, and microglia
Abstract
Keywords
Introduction
General principles of neuroglial development
Astrocytes
Generation and regulation of astrocyte precursors
Differentiation of APCs toward astrocytes
Specialization of astrocytes
What is the effect of development on astrocytic heterogeneity?
Astrocyte development in humans
Oligodendrocytes
Generation and regulation of oligodendrocyte precursors
Differentiation of OPCs toward oligodendrocytes
Specialization of oligodendrocytes
Potential other functions for OPCs?
Oligodendrocyte development in humans
Microglia
Generation and regulation of microglia progenitors
Differentiation of EMPs toward microglia
Specialization of microglia
Sex differences in microglia development
Microglia development in humans
How Do Glia–Glia Interactions Impact Glia Development?
Effects of neuroglia on OPC development and oligodendrocyte specialization
Astrocyte-microglia crosstalk during development
Understanding Neuroglial Development Shapes Novel Technologies
Acknowledgments
References
Chapter 4 Neuroglia in aging
Abstract
Keywords
Aging and the Brain
Aging of Astroglia
Molecular profile of aging astrocytes
Morphology
Physiology
Aging is Associated With Decline in Astroglial Support
Neurotransmitter homeostasis in aging
Neurogenesis
Neuroglio-vascular unit, glia limitans perivascularis, and the blood–brain barrier
Age-dependent decline of the glymphatic system
Age-dependent decline in astroglial metabolic support
Aging and astrocyte-based transmitophagy
Age-dependent decline in astrocyte-based cholesterol synthesis
Aging of Oligodendroglia
Aging of microglia
How to rejuvenate aged neuroglia
Conclusions
References
Chapter 5 Physiology of neuroglia of the central nervous system
Abstract
Keywords
Introduction: Neuroglia as Homeostatic and Defensive Arm of the CNS
Physiology of Astroglia
Diversity of astroglia
Complex Morphology of Protoplasmic Astrocytes
Resting membrane potential and ion distribution
Ion channels
Receptors to neurotransmitters and neuromodulators
Membrane transporters
Ionic signaling in astroglia
Physiology of Oligodendroglia
Physiology of oligodendrocytes
Physiology of adult oligodendroglial precursor cells
Physiology of Microglia
Membrane physiology
Microglial receptors
Calcium signaling in microglia
Conclusions
References
Chapter 6 Gliotransmission in physiologic and pathologic conditions
Abstract
Keywords
Gliotransmission in Physiological Conditions
Gliotransmission
Glutamate
d-serine
Role of tonic NMDAR currents in synaptic transmission
Role of tonic NMDAR currents in synaptic plasticity
Role of tonic NMDAR currents in cognitive functions
Tonic GABA current and neuronal excitability
Shunting inhibition of information processing
Synaptic transmission and plasticity
Summary of physiological function of tonic GABA
Gliotransmission in Psychiatric Disorders
Gliotransmission changes in major depression
Gliotransmission changes in bipolar disorder
Gliotransmission in schizophrenia
Gliotransmission in Neurological Diseases
Alzheimer disease
Parkinson disease
Epilepsy
Autism spectrum disorder
Conclusion
References
Chapter 7 Neuroglia and brain energy metabolism
Abstract
Keywords
Introduction
Role of Glia for Brain Energy Metabolism
ATP and Adenosine Metabolism
Glutamate, Glutamine, and GABA Metabolism
Role of Astrocyte-Neuron Lactate Shuttle
Seizure-Induced Impairment of Metabolism
Metabolic and Epigenetic Changes in Epilepsy
Metabolic Therapies
Therapeutic Manipulation of Astrocytic Adenosine Metabolism
Adenosine for Epilepsy Prevention
Astrocyte energy (dys)regulation in Neurodegenerative Diseases
Conclusions and Perspectives
Conflict of interest statement
References
Chapter 8 Neuroglia and the blood–brain barrier
Abstract
Keywords
Introduction to the Blood–Brain Barrier
Structure of the BBB
Development of the blood–brain barrier
Function and dysfunction of the BBB
Influence of Neuroglia and Mural Cells on the Blood–Brain Barrier
Astrocytes
Pericytes
Microglia
Oligodendrocytes/oligodendrocyte progenitor cells
Modeling the Blood–Brain Barrier
In vivo models
In vitro models
Conclusion
References
Chapter 9 Metabolic control of microglia in health and disease
Abstract
Keywords
Metabolic Regulation of Immune Cells
Metabolic Reprogramming: When and Why
Major Intracellular Metabolic Pathways and Their Influence on Microglial Function
Glucose and Glycolysis
Lactate and Lactate Metabolism
Pentose Phosphate Pathway
Fatty Acid Oxidation and Synthesis
Cholesterol Metabolism
Ketone Bodies
Amino Acids
Tricarboxylic Acid Cycle
Electron Transport Chain or Electron Transport System
Concluding Remarks and Future Perspectives
References
Chapter 10 The glymphatic system
Abstract
Keywords
Introduction
Historical Perspective and Discovery
The Glymphatic System in Health and Neurologic Diseases
Aging
Sleep
Edema
Alzheimer Disease
Parkinson Disease
Huntington Disease
Amyotrophic Lateral Sclerosis
Small Vessel Disease (Hypertension)
Hydrocephalus
Migraine
Stroke
Traumatic Brain Injury
Psychiatric Disorders
Clinical Imaging Tools for the Study of Glymphatic Function
Future Directions in Glymphatic System Research
Conclusion
References
Chapter 11 Neuroglia and the microbiota-gut-brain axis
Abstract
Keywords
Introduction
Glial Cells and the Microbiota-Gut-Brain Axis
Astrocytes and the Microbiota-Gut-Brain Axis
Astrocytes, the microbiota-gut-brain axis and disease
Microglia and the Microbiota-Gut-Brain Axis
GF status impairs microglia across the lifespan
Antibiotic treatment impairs microglia across the lifespan
Microbial metabolites regulate microglia
Microglia, the microbiota-gut-brain axis and disease
Oligodendrocytes and the Microbiota-Gut-Brain Axis
The gut microbiota restricts myelination
The gut microbiota promotes myelination
The gut microbiota and myelination in disease
Enteric Glia and the Microbiota-Gut-Brain Axis
GF status alters enteric glial cells
Antibiotic treatment alters enteric glial cells
Probiotic supplementation alters enteric glial cells
Microbial metabolite supplementation alters enteric glial cells
The gut microbiota and enteric glia in disease
Conclusions and Future Directions
Acknowledgments
References
Chapter 12 Neuroglia and extracellular matrix molecules
Abstract
Keywords
Introduction
ECM and Its Cellular Sources
Perineuronal Nets
ECM and Neuroplasticity
Astrocytes and Neurotransmission
Astrocytic Metabolism and Neuronal Activity
Relationship of Microglia With ECM Remodeling and Synaptic Plasticity
Tripartite Interactions Between Neurons, Glia, and ECM in Neuroplasticity
ECM Alterations and Reactive Gliosis in Neurologic Diseases
References
Chapter 13 In vitro models for human neuroglia
Abstract
Keywords
Introduction
Astrocytes
Oligodendrocytes
Microglia
Schwann Cells
Enteric Glia
Conclusion
Acknowledgment
References
Chapter 14 Animal-based approaches to understanding neuroglia physiology in vitro and in vivo
Abstract
Keywords
Introduction
Mammalian Animal Models: Mus musculus and Rattus norvegicus
The Impact of Primary Cell Cultures
Culturing primary astrocytes: Methods, challenges, and advancements in selectivity
In vitro microglial cultures: Evolution, limitations, and innovative approaches
In vitro studies on oligodendrocyte-lineage cells: Isolation, maturation, and coculturing with neurons
Generation of constitutive knock-out models for in vivo glia research
Genetic manipulations in mice_ The impact of GFAP and IP3R2 knock-outs on astrocytic function and Ca2+ signaling
Impact of CSF1R deficiency on microglial development and maintenance in mice and rats
Impact of oligodendrocyte-lineage gene knock-outs on axonal physiology and myelination
Conditional Knock-Out Models: Overcoming Limitations of Constitutive Knock-Outs in Neuroscience Research
Conditional knock-out models: Targeting astrocyte-specific genes with precision
Refining microglial manipulation in neuroscience research: Challenges and solutions
Optimizing oligodendrocyte-specific genetic interventions: Challenges and opportunities
Transgenic Split-Cre complementation for the study of glial cells
Conditional Knock-Out Models With Temporal Control
Refining astrocyte-specific gene manipulation: The role of CreERT2/loxP system in neuroscience research
Refining microglia-specific manipulations: Overcoming limitations in current CreERT2 systems
Targeting oligodendrocyte-lineage cells in the CNS: Recent advances and considerations for experimental design
Constitutive and Conditional Expression of Reporter Genes
Astrocyte-specific fluorescent protein expression and its applications in neuroscience research
Exploring the heterogeneity of microglia: A comprehensive review of transgenic lines and techniques
Utilizing fluorescent protein expression systems to investigate oligodendrocyte-lineage cell physiology and fate
The Advantages of Viral Gene Transduction
Optimizing viral gene delivery to astroglia for precise transgene expression and minimal interference
Enhancing viral-mediated gene transfer efficiency in microglia for targeted transgene expression
Enhancing viral transduction efficiency for targeting oligodendroglia
Using the Versatility of Zebrafish as a Model System for Studying CNS Development and Glial Physiology
Radial astroglia in zebrafish: Functions and characteristics
Microglial dynamics and function in zebrafish CNS development
Insights into oligodendrocyte development and myelination dynamics in zebrafish
Exploring Glial Physiology and Disease Susceptibility in Drosophila melanogaster
Astrocyte-like glia in Drosophila: A comprehensive molecular comparison and functional overview
Conclusion
Conflict of interest
References
Chapter 15 Single-cell omics and heterogeneity of neuroglial cells
Abstract
Keywords
Introduction
Single-Cell Transcriptomic Technologies and Cell Diversity in the CNS
Spatial Transcriptomic Methods to Map the Organization of Cell Diversity
Revealing Neuroglial Cell Diversity Using scRNA-Seq and Spatial Transcriptomic Approaches
Microglia
Oligodendrocytes and oligodendrocyte progenitor cells (OPCs)
Astrocytes
Using Transcriptomics to Understand Neuroglial Cell Changes Across the Lifespan: A Focus on Astrocytes
Conclusion and Future Perspectives
References
Chapter 16 Imaging neuroglia
Abstract
Keywords
Introduction
Microscopic Imaging
In vivo microscopic imaging
Noninvasive In Vivo Imaging
PET imaging of neuroglia
MRI imaging of neuroglia
Concluding remarks on noninvasive in vivo imaging
Conclusion
References
Index

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

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

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

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Neuroglia in the Healthy Nervous System, Part I

Purchase options

World Book Day Celebration!

Institutional subscription on ScienceDirect

Elly M. Hol

Lotje D. De Witte

Eleonora Aronica

Alexei Verkhratsky

Related books