Neuroglia: Function and Pathology by Alexei Verkhratsky and Arthur M. Butt

Abstract

“Glial cells are in the brain to support neurons” is one of the commonplaces taught at regular lectures by neuroscientists to future generations of neurobiologists. Never mind that detailed insights into glial physiology and pathobiology are usually neglected in thematic neuroscience curricula. Indeed, the classic bias in the field of neuroscience comes from the term “neuro” itself. General thinking dictates that when one can manipulate specific subtypes of neurons distinguished by a signature of probably a handful of molecules at millisecond precision chemically or by light, and receive a behavioral response from the experimental organism, be this invertebrate or vertebrate, then neurons alone shall be sufficient to organize the brain's output. We could not be more wrong and on an arduous journey to fundamentally misinterpret brain operations if holding onto these views. It is time to acknowledge the contribution of other cell types, cumulatively termed “neuroglia,” with astroglia, oligodendroglia, and microglia being present in the central nervous system alone. Adding Schwann cells, satellite glia, enteric glia, and glial cells of sensory organs to this list is a thrilling reminder that an amazing variety of glial cell types not only exists at around 1:1 ratio but works in unison in the human nervous systems to allow it to reach its computational, intellectual, and emotional power that makes us unique.

“Would you know a renown ‘glioscientist’ as if a neuroscientist?” For many, this could be an unexpectedly challenging question still. Here, we introduce Alexei Verkhratsky and Arthur M. Butt as two of the most eminent glia biologists of our time whose new book, titled “Neuroglia: Function and Pathology” is a wonderfully illustrated, comprehensive, thematic, and insightful account of the vast knowledge that has accumulated on glial cells of both the central and peripheral nervous systems over the past ~150 years. This book, the newest in a series of compendia on glial cells,^1-4 is educational for it systematically summarizing the origins, development, anatomy, molecular make-up, membrane biophysics, cellular interactions, and functions in relation to nerve cells and the broader brain homeostasis of each major glial cell type. Yet, it is an enticing read that also answers many unexpected questions ranging from the history of neuroscience (e.g., “do you know who coined the word astrocyte?”) to debunking some of the most pressing dogmas, like the number of neurons versus other cells in the brain. To this point, and using even evolutionary biology, a ~ 1:1 neuron: astrocyte ratio is formulated, which could work well if one considers that each neuron could have its “personal” caretaker, which supports, interacts, facilitates, removes waste, and even protects against disease and demise.

Neuroglia: Function and Pathology starts with a historical account of discoveries that shaped this field, continues with the in-depth narration of neuroglia physiology, and seamlessly flows to the detailed description of the defining roles of neuroglia in brain diseases. Its part on physiology embraces all types of glia, be these either central or peripheral, and provides an exciting picture of these highly heterogeneous cells in form and function: It goes on to highlight that the ability of constant change amongst glia provides the basis of lifelong adaptation of the nervous system. On astrocytes, we learn that learning, memory, or neural plasticity, phenomena that are commonly assigned to neurons, simply cannot take place without them. Likewise, it is sobering to realize that neurons are incapable of producing their acting tools, the two major amino acid neurotransmitters (whether glutamate or GABA) without astrocytes supplying them with glutamine, the obligatory precursor of both chemical messengers. Similarly, astrocytes support synaptogenesis and synapse integrity. When this function fails, synaptic plasticity is eliminated. On microglia, the concept of synapse turnover is exemplified, which is the dynamic cycle of synapses being born, maintained if used, and then removed. If synaptic pruning by microglia is affected, then the neurocircuits neither develop nor function properly. Instead, the brain consumes massive amounts of excess energy, the production of which is inevitably associated with oxidative stress. And astrocytes are the foremost cell type to protect against oxidative stress by producing the bulk of glutathione, its scavenger.

Glutamate, however powerful as an excitatory neurotransmitter, is even more powerful as a natural poison that kills by producing a state of excitotoxicity for neurons. It is therefore not entirely unexpected that silencing glutamate clearance by astrocytes effectively tarnishes the brain. This and many similar fundamental homeostatic actions make neuroglia central to neuropathology: every disease is a homeostatic challenge. When homeostatic cells of the nervous system cannot meet a challenge, then the nervous system cannot survive. Despite the “neurocentric” views of modern-day neurology, this book reinforces the observation that neuroglia defines neuronal survival, neuronal protection, postlesion regeneration, and tissue rehabilitation. In other words, Verkratsky and Butt make it plain obvious that neuroglia defines the resilience of the nervous system. Accordingly, the decline of neuroglia accompanies aging, thus opening the gate for neurodegeneration, which limits cognitive longevity. It is commendable, therefore, that the second part of Neuroglia: Function and Pathology provides breathtaking insights into brain diseases, be these sporadic or inherited in origin, and includes pathological aging/neurodegeneration, mental illnesses, neurodevelopmental disorders, toxic encephalopathies, pain, viral infections, and cancer, to contextualize all that is said about the anatomy and function of glial cells populating the brain, as well as the peripheral nervous system.

This new book shall undoubtedly find its way onto the bookshelves of the researchers working on glia biology because of its attention to detail, and depth of insight. But it shall equally be sought after by students of all ages because of it being an entertaining read and an educational summary of digestible bouts of information for anyone who needs to look up a specific feature of a certain glial cell type. In the age of Google, this book will still stand firm because of its completeness, conceptualization, and being exceptionally well-referenced for all its facts and figures. Therefore, and regardless of using its paper print or online document version, we will certainly be among those relying on its vast content for our own work until the next iteration^1-3 will come about.

Tibor Harkany and Tomas Hökfelt co-wrote this editorial.

This work was supported by the Swedish Research Council (2020-01688, T.Hö.; 2018-02838; T.Ha.); The Arvid Carlsson Foundation (T.Hö.), the Swedish Brain Foundation (Hjärnfonden, FO2020-0178, T.Ha.), the Novo Nordisk Foundation (NNF20OC0053667, T.Ha.), and the European Research Council (FOODFORLIFE, ERC-2020-AdG-101021016; T.Ha.).

There is no conflict of interest.