Glial Physiology and Pathophysiology E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 968

Veröffentlichungsjahr: 2013

Beschreibung

Glial Physiology and Pathophysiology provides a comprehensive, advanced text on the biology and pathology of glial cells.

Coverae includes:

• the morphology and interrelationships between glial cells and neurones in different parts of the nervous systems
• the cellular physiology of the different kinds of glial cells
• the mechanisms of intra- and inter-cellular signalling in glial networks
• the mechanisms of glial-neuronal communications
• the role of glial cells in synaptic plasticity, neuronal survival and development of nervous system
• the cellular and molecular mechanisms of metabolic neuronal-glial interactions
• the role of glia in nervous system pathology, including pathology of glial cells and associated diseases - for example, multiple sclerosis, Alzheimer's, Alexander disease and Parkinson's

Neuroglia oversee the birth and development of neurones, the establishment of interneuronal connections (the 'connectome'), the maintenance and removal of these inter-neuronal connections, writing of the nervous system components, adult neurogenesis, the energetics of nervous tissue, metabolism of neurotransmitters, regulation of ion composition of the interstitial space and many, many more homeostatic functions. This book primes the reader towards the notion that nervous tissue is not divided into more important and less important cells. The nervous tissue functions because of the coherent and concerted action of many different cell types, each contributing to an ultimate output. This reaches its zenith in humans, with the creation of thoughts, underlying acquisition of knowledge, its analysis and synthesis, and contemplating the Universe and our place in it.

• An up-to-date and fully referenced text on the most numerous cells in the human brain
• Detailed coverage of the morphology and interrelationships between glial cells and neurones in different parts of the nervous system
• Describes the role og glial cells in neuropathology
• Focus boxes highlight key points and summarise important facts
• Companion website with downloadable figures and slides

Leseprobe

Contents

Cover

Title Page

Copyright

Dedication

Preface

About the Authors

Abbreviations

About the Companion Website

Chapter 1: History of Neuroscience and the Dawn of Research in Neuroglia

1.1 The Miraculous Human Brain: Localising the Brain Functions

1.2 Cellular Organisation of the Brain

1.3 Mechanisms of Communications in Neural Networks

1.4 The Concept of Neuroglia

1.5 Beginning of the Modern Era

1.6 Concluding Remarks

References

Chapter 2: General Overview of Signalling in the Nervous System

2.1 Intercellular Signalling: Wiring and Volume Modes of Transmission

2.2 Cellular Signalling: Receptors

2.3 Intracellular Signalling: Second Messengers

2.4 Calcium Signalling

2.5 Concluding Remarks

Chapter 3: Neuroglia: Definition, Classification, Evolution, Numbers, Development

3.1 Definition of Neuroglia as Homeostatic Cells of the Nervous System

3.2 Classification

3.3 Evolution of Neuroglia

3.4 Numbers: How many Glial Cells are in the Brain?

3.5 Embryogenesis and Development of Neuroglia in Mammals

3.6 Concluding Remarks

References

Chapter 4: Astroglia

4.1 Definition and Heterogeneity

4.2 Morphology of the Main Types of Astroglia

4.3 How to Identify Astrocytes in the Nervous Tissue

4.4 Astroglial Syncytial Networks

4.5 Physiology of Astroglia

4.6 Functions of Astroglia

4.7 Concluding Remarks

References

Chapter 5: Oligodendrocytes

5.1 Oligodendrocyte Anatomy

5.2 Myelin Structure and Function

5.3 Physiology of Oligodendrocytes

5.4 Oligodendrocyte Development

5.5 Concluding Remarks

References

Chapter 6: NG2–glial Cells

6.1 Definition of NG2-glia

6.2 Structure of NG2-glia

6.3 Physiology of NG2-glia

6.4 Proliferation of NG2-glia and Generation of Oligodendrocytes

6.5 Relationship between NG2-glia and CNS Pericytes

6.6 Evolution of NG2-glia

6.7 Concluding Remarks

References

Chapter 7: Microglia

7.1 Definition of Microglia

7.2 Microglial Origin and Development

7.3 Morphology of Microglia

7.4 General Physiology of Microglia

7.5 Microglial Migration and Motility

7.6 Physiological Functions of Microglia: Role in Synaptic Transmission and Plasticity

7.7 Microglia in Ageing

7.8 Concluding Remarks

References

Chapter 8: Peripheral Glial Cells

8.1 Peripheral Nervous System

8.2 Schwann Cells

8.3 Satellite Glial Cells

8.4 Enteric Glia

8.5 Olfactory Ensheathing Cells (OECs)

8.6 Concluding Remarks

References

Chapter 9: General Pathophysiology of Neuroglia

9.1 Neurological Disorders as Gliopathologies

9.2 Reactive Astrogliosis

9.3 Wallerian Degeneration

9.4 Excitotoxic Vulnerability of Oligodendrocytes: The Death of White Matter

9.5 Activation of Microglia

9.6 Concluding Remarks

References

Chapter 10: Neuroglia in Neurological Diseases

10.1 Introduction

10.2 Genetic Astrogliopathology: Alexander Disease

10.3 Stroke and Ischaemia

10.4 Migraine and Spreading Depression

10.5 CNS Oedema

10.6 Metabolic Disorders

10.7 Toxic Encephalopathies

10.8 Neurodegenerative Diseases

10.9 Leukodystrophies

10.10 Epilepsy

10.11 Psychiatric Diseases

10.12 Autistic Disorders

10.13 Neuropathic Pain

10.14 Demyelinating Diseases

10.15 Infectious Diseases

10.16 Peripheral Neuropathies

10.17 Gliomas

10.18 Concluding Remarks

References

Author Index

Subject Index

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Library of Congress Cataloging-in-Publication Data

Verkhratskii, A. N. (Aleksei Nestorovich)

Glial physiology and pathophysiology : a handbook / Alexei Verkhratsky and Arthur Butt.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-470-97852-8 (cloth) – ISBN 978-0-470-97853-5 (pbk.)

I. Butt, Arthur. II. Title.

[DNLM: 1. Neuroglia–physiology. 2. Nervous System Diseases–physiopathology. 3. Neuroglia–pathology. WL 102]

612.8′1046–dc23

2012034773

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Dedicated to our families

Preface

In 2007, we published the first textbook on glial neurobiology, Glial Neurobiology: A Textbook. The aim of our first book was to provide an introduction to glial cells, aimed at undergraduates and postgraduates in neuroscience. However, it has become clear to us that there is also the need for a more detailed and comprehensively referenced account of glial neurobiology for researchers and clinicians. This is the aim of our new book, Glial Physiology and Pathophysiology. We have deliberately shaped this to be a textbook that is readily accessible to those who want to get a systematic view on neuroglial function in physiology and pathophysiology.

This is meant to be a learning resource, not a reference book. The glial field has a weighty reference book, Neuroglia, written by several dozen experts in the different aspects of glial cell biology under the auspices of H. Kettenmann and B. Ransom. However, a substantial gap exists between the reference book Neuroglia and our first book Glial Neurobiology: A Textbook, both in the scientific content and complexity. The aim of our new book Glial Physiology and Pathophysiology is to fill this gap and to provide an account of glial cell biology that, hopefully, is written in a style that is enjoyable and interesting to read.

Our purpose has been to write a comprehensive, yet concise and readable, account of neuroglia – the class of cells that provide for the housekeeping and defence of the nervous system. Neuroglial functions in health and disease are generally overlooked in contemporary curricula for medics and biologists. Indeed, neuroglia are mentioned only superficially in the absolute majority of university courses. This neglect has been developed over the course of the last century or so, mainly after the discovery of electrical excitability in neurones, the principal signalling cells in the nervous system. The discovery of action potentials and synaptic transmission provided us with a fundamental understanding of nervous system functioning; neuronal networks can be relatively easily reduced to logical units communicating in binary fashion, and electronic summation provides a simple tool to predict how the excitation/inhibition of a given neurone defines output. This has had a mesmerising effect upon the minds of neurophysiologists. We can see the most powerful computers in the world employed to model the brain, based on an assumption of the primary role for action potential-mediated binary encoded signalling between logical elements that can exist in a limited (excited/resting/inhibited) number of states.

Nature, of course, is far more complex than our most ingenious engineering. The nervous system is not a computer, with an output that can be precisely calculated. There are many ways of signalling between neural cells that involve diffusion of many different molecules, each with their own targets, weaving an intricately interconnected canvas for information processing.

This book is not about processing in neural networks, but rather about overall homeostasis in the nervous system. Homeostasis is fundamental for the life of organisms, organs, tissues and cells. The nervous system is not an exception. In the course of the evolution of the nervous system that appeared in the most primitive multicultural organisms, neural cells have divided into the executive branch, represented by neurones (which control reception of sensory input and effect an output to control peripheral organs) and the housekeeping branch, represented by neuroglia. Perfection of fast signalling in neuronal networks required a division of labour, and neurones lost their ability to maintain their own survival adequately; these functions went to neuroglia.

This, then, was our endeavour – to relate the evolutionary history of neuroglia and to demonstrate how these cells assume every conceivable function aimed at maintaining nervous system homeostasis. Indeed, neuroglia oversee the birth and development of neurones, the establishment of inter-neuronal connections (the ‘connectome’), the maintenance and removal of these inter-neuronal connections, wiring of the nervous system components, adult neurogenesis, the energetics of nervous tissue, metabolism of neurotransmitters, regulation of ion composition of the interstitial space and many, many more homeostatic functions.

In this book, we start with the history of neuroscience, trying to show the development of ideas and concepts of nervous system organisation. In particular, we emphasise that, from the very beginning of cellular neuroscience, little distinction was made between neural cell types and the great minds of neuroscience regarded glia as an indispensable element of the neural architecture. By doing this, we hope to prime the reader towards the notion that nervous tissue is not divided into ‘more important’ and ‘less important’ cells. The nervous tissue functions because of the coherent and concerted action of many different cell types, each contributing to an ultimate output. This reaches its zenith in humans, with the creation of thoughts, underlying acquisition of knowledge, its analysis and synthesis, and contemplating the Universe and our place in it.

Also, we contemplate the role of neuroglia in pathology. All diseases are, fundamentally, failures of the homeostasis that makes organs and organisms incompatible with life. The neurological diseases are, ipso facto, failures of homeostasis in the nervous tissue and are, in essence, failures of the homeostatic cells – neuroglia. Indeed, progression and outcome of all neurological diseases are defined by neuroglia, which defends the brain. When this defence system crumbles, the nervous tissue dies.

This book has been shaped by many years of work and discussions with our friends and colleagues, to whom we extend our heartfelt thanks. Also, in writing this book we have relied on many authoritative papers and review articles written by those who are more expert than ourselves in particular aspects of glial cell biology. We hope that we have done a good job in representing their findings. We apologise for any inaccuracies and for any important omissions, which we trust are few.

Alexei VerkhratskyArthur ButtJune 20, 2012

About the Authors

Alexei Verkhratsky

Professor Alexei Verkhratsky, MD, PhD, D.Sc., Member of Academia Europaea, Member of Real Academia Nacional de Farmacia, was born in 1961 in Stanislav, Galicia, Western Ukraine. He graduated from Kiev Medical Institute in 1983 and received his PhD (1986) and D.Sc. (1993) in Physiology from Bogomoletz Institute of Physiology, Kiev, the Ukraine. From 1990 to 1995, he was Head of the Laboratory of Cellular Signalling in Bogomoletz Institute of Physiology.

In the period between 1989 and 1995, Professor Verkhratsky was visiting scientist in Heidelberg and Gottingen, and between 1995 and 1999 he was a research scientist at Max Delbrück Centre of Molecular Medicine in Berlin. He joined the Division of Neuroscience, School of Biological Sciences in Manchester in September 1999, became a Professor of Neurophysiology in 2002 and served as head of the said division from 2002 to 2004. From 2007 to 2010, he was appointed as Visiting Professor/Head of Department of Cellular and Molecular Neurophysiology at the Institute of Experimental Medicine, Academy of Sciences of Czech Republic. In 2010, he was appointed as a Research Professor of the Ikerbasque (Basque Research Council), and in 2011 as a Visitor Professor at Kyushu University, Fukuoka, Japan.

Professor Verkhratsky was elected to membership of Academia Europaea in 2003, and since 2006 he has been Chairman of the Physiology and Medicine section. In 2011, he was elected a foreign member of Real Academia Nacional de Farmacia, Spain. He is editor-in-chief of Cell Calcium (2000) and Membrane Transport & Signalling – Wiley Interdisciplinary Reviews (2009), Receiving Editor (neuroscience) of Cell Death & Disease (2009) and a member of the editorial boards of Pflugers Archiv European Journal of Physiology, Journal of Molecular & Cellular Medicine, Acta Physiologica (Oxford), Acta Pharmacologica Sinica (2005), Glia (2008), Frontiers in Neuropharmacology, Frontiers in Aging Neuroscience, (2009), Purinergic Signalling, ASN Neuro (2010), Neuroscience Bulletin (2011). He has delivered more than 180 international invited lectures and seminars.

Professor Verkhratsky is an internationally recognised scholar in the field of cellular neurophysiology. His research is concentrated on the mechanisms of inter- and intracellular signalling in the central nervous system, being especially focused on two main types of neural cells, on neurones and neuroglia. He has made important contributions to understanding the chemical and electrical transmission in reciprocal neuronal-glial communications and on the role of intracellular calcium ion signals in the integrative processes in the nervous system. Many of his studies are dedicated to investigations of cellular mechanisms of neurodegeneration.

In collaboration with Dr. P. Fernyhough, Professor Verkhratsky demonstrated that experimental diabetes is associated with disruption of Ca2+ homeostasis and mitochondrial function; both of these systems appear to be regulated by insulin-receptor-dependent signalling cascades. He was the first to perform intracellular Ca2+ recordings in old neurones in isolation and in situ, which provided direct experimental support for the ‘Ca2+ hypothesis of neuronal ageing’. In recent years, in collaboration with Professor J. J. Rodriguez, he has been studying glial pathology in Alzheimer's disease. He is the author of a pioneering hypothesis of astroglial atrophy as a mechanism of neurodegeneration.

Professor Verkhratsky has authored and edited ten books, edited 19 special issues and published approximately 300 papers and chapters. His papers have been cited more than 8,500 times (H-index 53).

Arthur Butt

Professor Arthur Butt has worked on glial cells for over 25 years, using multiple cell biological, molecular, anatomical and physiological techniques. He received his PhD from King's College, London in 1986, working with Joan Abbott, a leader in blood-brain barrier research. After a postdoctoral position in the lab of Ed Liebermann (North Carolina, USA) and a Grass Fellowship at the Wood's Hole Marine Laboratories, he joined the lab of Bruce Ransom (Yale University, USA). Here, he began his work on glial cells in the optic nerve, and he has pursued this line of research ever since.

Professor Butt obtained his first position in Guy's and St Thomas's Hospitals Medical Schools in 1990, where he worked closely with Martin Berry, a leader in CNS regeneration studies. After gaining a personal chair in King's College London in 2000, Professor Butt moved to the University of Portsmouth in 2005, where he is currently Director of the Institute of Biomedical and Biomolecular Sciences. Professor Butt is closely associated with the Anatomical Society, in which he sat on the management committee and served as programme secretary for many years. He is on the editorial board of Glia, has acted as guest editor for a number of special issues for the Journal of Anatomy, and edited the first special issue on novel NG2-glial cells for the Journal of Neurocytology in 2000.

Much of Professor Butt's work has focused on oligodendrocytes, using the model tissue of the rodent optic nerve, on which he has published a number of reviews and book chapters. He has focused on the fundamental biology of glial cells, with a particular relevance to multiple sclerosis and neurodegeneration. In this regard, Professor Butt would like to thank especially the Multiple Sclerosis Society, the Anatomical Society and The International Spinal Research Trust, for their support over the years. He is also part of the European consortium Edu-Glia (2009–2013), which provided for the establishment of a European school for glial research training.

Abbreviations

AAarachidonic acidAββ-amyloid proteinα-ARα adrenergic receptorβ-ARβ adrenergic receptorA1–3adenosine receptor type 1–3ABCATP-binding cassetteACadenylate cycliseAChacetyl cholineAChBPacetylcholine binding proteinADAlzheimer's diseaseADNFactivity-dependent neurotrophic factorADPadenosine diphosphateAEPanterior entopeduncular areaAIDPacute inflammatory demyelinating neuropathyAIDSacquired immunodeficiency syndromeALSamyotrophic lateral sclerosis (“Lou Gehrig's disease” in USA)AMPAα-amino-3-hydroxy-5-methyl-4-isoxazolepropionateankGankyrinGANLSastrocyte–neurone lactate shuttleANPatrial natriuretic peptide4-AP4-amynopyridineAQPaquaporinARadrenergic receptorASICAcid Sensing Ion ChannelAT1/2angiotensin receptor type 1/2ATPadenosine triphosphateAxDAlexander diseaseBACE 1β-site APP-cleaving enzyme 1BBBblood-brain barrierBCboundary capbHLHbasic helix-loop-helixBDNFbrain-derived neurotrophic factorBMPbone morphogenetic proteinBPbinding proteinBzATP2′,3′-(benzoyl-4-benzoyl)-ATPcAMPcyclic adenosine 3′,5′-monophosphatecGMPcyclic guanosine 3′5′-monophosphateCAIIcarbonic anhydrase IICa2+Calcium ionCaMcalmodulinCaM kinasecalcium-calmodulin-dependent protein kinaseCaM ACcalcium-calmodulin-dependent-adenylate cyclaseCaM-phosphatasecalcium-calmodulin-dependent-protein phosphataseCaspcaspaseCaVvoltage operated Ca2+ channelCBcannabinoid receptorCBPCa2+ binding proteinsCCRchemokine receptorCdkcyclin-dependent kinaseCFTRcystic fibrosis transmembrane conductance regulator channelCGEcaudal ganglionic eminenceCGTceramide galactosyltransferaseCHNcongenital hypomyelinating neuropathyCICRcalcium-induced calcium releaseCIPDchronic inflammatory demyelinating neuropathyCLCchloride channelCLICchloride intracellular channelCMTCharcot Marie Tooth diseaseCMT1XX-linked Charcot Marie Tooth diseaseCNTFciliary neurotrophic factorCNQX6-cyano-7-nitroquinoxaline-2,3-dione (AMPA receptor antagonist)CNPase2′,3′-cyclic nucleotide-3′-phosphodiesteraseCNScentral nervous systemCOXcyclo-oxygenaseCRACCa2+-release activated Ca2+ channelCREBcyclic element-binding proteinCSFcerebrospinal fluidCSPGchondroitin sulphate proteoglycanCSTcerebroside sulfotransferaseCxconnexinCXCRchemokine receptorCysLTcysteinyl leukotrienesDaDaltonDAGdiacylglycerolD-AP5D-2-amino-phosphonopentanoic acid (NMDA receptor antagonist)DM20isoform of PLPDOPAdopamineDRGdorsal root ganglionDRP2dystroglycan-related protein 2EAATexcitatory amino acid transporterEAEexperimental autoimmune encephalomyelitisECMextracellular matrixECSextracellular spaceEGCenteric glial celleGFPenhanced green fluorescent proteinEGFRepidermal growth factor receptorEKequilibrium potential for potassiumEMelectron microscopyENACEpithelial Sodium ChannelENCCEnteric Neural Crest CellENSenteric nervous systemEphephrinEPSCexcitatory postsynaptic currentERKextracellular signal-regulated protein kinaseETendothelinFDGFluorodeoxyglucoseFGF2fibroblast growth factor 2FGFRFGF receptorfMRIfunctional magnetic resonance imagingGABAγ-aminobutyric acidGABA-TGABA transaminaseGADglutamate decarboxylaseGalCgalactocerebrosideGATGABA transporterGCguanylate cycliseGPCRG-protein coupled receptorGDAPganglioside-induced differentiation-associated proteinGDNFglial-derived neurotrophic factorGFAPglial fibrillary acidic proteinGFPgreen fluorescent proteinGIgastrointestinalGJgap junctionGLASTglutamate/aspartate transporterGLT-1glutamate transporter-1GluA1-4AMPA receptor subunitsGluK1-3kainite receptor subunitsGluN1-3NMDA receptor subunitsGluRglutamate receptorGlyTglycine transporterGnRHgonadotropin-releasing hormoneGRPglial restricted precursorGSNOS-nitrosoglutathioneGSK3βGlycogen synthase kinase 3β2-HETE2-hydroxyeicosatetraenois acid5-HT5 hydroxy tryptamine (serotonin)H1–3histamine receptor type 1–3HADHIV-1 associated dementiaHDHuntington's diseaseHDACHDACHIPKhomeodomain interacting protein kinaseHIVimmunodeficiency virusHIVEHIV-encephalitisHNPPhereditary neuropathy with liability to pressure palsiesHTLV-1Human T-lymphotropic virus type-1IFNinterferonIGFinsulin-like growth factorIGIFinterferon inducing factoriGluRionotropic glutamate receptorILinterleukinInsP3inositol-trisphosphateInsP3Rinositol-trisphosphate receptorsIPCintermediate progenitor cellJAKJanus kinaseJAMjunctional adhesion moleculeJNKc-Jun N terminal kinaseKAkainatekDakilo DaltonKArapidly inactivating A-type K+ channelKDdelayed rectifier K+ channelKCacalcium-activated K+ channelKirinward rectifier K+ channel[K+]iintracellular K+ concentration[K+]oextracellular K+ concentrationLDHlactate dehydrogenaseLEFlymphoid enhancing factorLes/Lslate endosomes/lysosomesLGElateral ganglionic eminenceLIFleukaemia-inhibitory factorL-MAGlarge isoform of myelin associated glycoproteinLN2Laminin 2LPSlypopolysaccharideLTPlong-term potentiationmChRmuscarinic cholinoreceptorMAGmyelin associated glycoproteinMAPmicrotubule associated proteinMAPKmitogen-activated protein kinaseMBPmyelin basic proteinM-CSFRmacrophage colony-stimulating factor receptorMCTmonocarboxylase transporterMEKmitogen-activated/extracellular regulated kinaseMGEmedial ganglionic eminencemGluRmetabotropic glutamate receptormiRNAmicroRNAMLCMegalencephalic leukoencephalopathy with subcortical cystsMOBPmyelin-associated/oligodendrocyte basic proteinMOGmyelin oligodendrocyte proteinMOSPmyelin/oligodendrocyte specific proteinMPNmedial preoptic nucleusMPTPmitochondrial transition permeability poreMRFMyelin gene regulatory factorMRImagnetic resonance imagingMRSmagnetic resonance spectroscopyMSmultiple sclerosisMSAmultiple system atrophymTORmammalian target of rapamycinNAADPNicotinic acid adenine dinucleotide phosphateNADPHNicotinamide adenine dinucleotide phosphate[Na+]iintracellular Na+ concentrationNaVvoltage-gated Na+ channelnAChRnicotinic cholinoreceptorNBCsodium-bicarbonate transporterNCAMneural cell adhesion moleculeNCCneural crest cellNCSCneural crest stem cellNCXsodium-calcium exchangerNDPasenucleoside diphosphataseNFneurofascinNF-κBnuclear factor κBNGFnerve growth factorNgRNogo receptorNHEsodium-hydrogen exchangerNK-1neurokinin-1 receptor (substance P receptor)NKAsodium-potassium pump (Na+/K+ ATPase)NKCCsodium-potassium-chloride cotransporterNMDAN-methyl-D-aspartateNMONeuromyelitis optica (Devic's disease)NONitric oxideNOSnitric oxide synthaseNPneural precursorNRGneuregulinNSCneural stem cellNTneurotrophinNTDPasenucleoside triphosphate diphosphohydrolaseOEColfactory ensheathing cellOlig1/2oligodendrocyte lineage transcription factor 1/2OMgpoligodendrocyte-myelin glycoproteinOPColigodendrocyte progenitor cellOSP/claudin-11oligodendrocyte specific proteinOVLTorganum vasculosum of the lamina terminalisP0peripheral myelin protein zeroP2peripheral myelin protein 2PAFplatelet-activating factorPARprotease-activated receptorsPDParkinson's diseasePDGFplatelet-derived growth factorPDGFRαplatelet-derived growth factor receptor alphaPDGFRβplatelet-derived growth factor receptor betaPDSparoxysmal depolarization shiftPETpositron emission tomographyPGE2prostaglandin E2PGKphosphoglycerate kinasePIP2phosphatidylinositol (4,5)-biphosphatePIP3phosphatidlyinositol (3,4,5)-triphosphatePKAprotein kinase APKCprotein kinase CPLCphospholipase CPLPproteolipid proteinPMCAplasmalemmal Ca2+ ATP-asePMP22peripheral myelin protein 22PNPasepurine nucleoside phosphorylasePNSperipheral nervous systemPOApro-oligodendroblast antigenPSDpost-stroke dementiaPTENPhosphatase and tensin homologuePTPpermeability transition poreRMPresting membrane potentialRMSrostral migratory streamROSreactive oxygen speciesRTKreceptor tyrosine kinaseRyRRyanodine receptorRVDregulatory volume decreaseSCIspinal cord injurySCNSuprachiasmatic NucleiSCPSchwann cell precursorSDSleep deprivationSERCASarco(Endo)plasmic Reticulum Ca2+ ATP-asesSGCsatellite glial cellShhsonic hedgehogαSMAα-smooth muscle actinS-MAGsmall isoform of myelin associated glycoproteinSNAPsynaptosome-associated protein (e.g. 25 kDa SNAP25)SNAREsoluble N-ethyl maleimide-sensitive fusion protein attachment protein receptorSNATsodium-coupled neutral amino acid transporterSOCCstore-operated Ca2+ channelsSOCEstore-operated Ca2+ entrySTATSignal Transducers and Activators of TranscriptionSUCNRsuccinate receptorSVZsubventricular zoneTCAtricarboxylic acidTEAtetraethylammoniumTftransferrinTGFtransforming growth factorTJtight junction7-TM7 transmembrane receptorTCFT-cell factorTLRToll-like receptorTNFtumour necrosis factorTNFRTNF receptorTRP channelTransient receptor potential channelTSP-1thrombospondinTZtransition zoneTTXtetrodotoxinVAMP2vesicle-associated membrane protein 2 (synaptobrevin 2)V-ATPasevacuolar V-type proton ATPaseVEGFvascular endothelial growth factorVGlutTvesicular glutamate transporterVIPvasoactive intestinal peptideVPACVIP/pituitary adenylate cyclase-activating peptide receptorVmmembrane potentialVNUTvesicular nucleotide transporterVOCCvoltage-operated Ca2+ channelVRACvolume-regulated anion channelVSOACvolume-sensitive organic anion channelVSORvolume-sensitive outwardly rectifying channelVTVolume Transmission (used only in Chap 1 – so omit?)VWMVanishing white matter diseaseVZventricular zoneWTwiring transmission (used only in Chap 1 – so omit?)YY1Yin Yang 1ZnTplasmalemmal Zn2+ transporter

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www.wiley.com/go/verkhratsky/glialphysiology

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1

History of Neuroscience and the Dawn of Research in Neuroglia

1.1 The Miraculous Human Brain: Localising the Brain Functions

‘Many things seem miraculous until you understand them and some are so marvellous you could call them miracles.'

Merlin to young Arthur (Crossley-Holland, 2009)

Human brain and human intellect – these are still miraculous for us. The scientific endeavours driven by human curiosity have deciphered many miracles of nature. Yet our understanding of how we think, and where lies the fundamental mechanism that distinguishes a man from a beast, remains obscure and hazy.

The general concept that brain functions are produced by immensely complex structures localised in the brain parenchyma evolved slowly over history. In the most ancient times, the place for sprit, thoughts and cognition was believed to be associated with the heart, and this was considered to be the hegemonic organ by the Hebrews, the Mesopotamians, the Indians, the Egyptians and possibly the Chinese (Gross, 1995). The ‘cardiocentric’ doctrine was contemplated by ancient Greeks, who were the first to apply logic, scepticism and experimentation to understand the forces that drive the world and life. Possibly, it all began in about the 7th century BC, when Thales of Miletus made the fundamental discovery that our world is mostly made of water, a statement which, at least as far as life is concerned, remains undisputable. Slightly later, Empedocles broadened the list of basic elements of nature to earth, air, fire and water, and Democritus (460–370 BC) introduced the atomic theory, in which all differences between substances was determined by their atoms and inter-atomic relations. More or less at the same time, the idea of a special substance composed of air and vapours, the thymós or pneuma, which represents the substance of life, came into existence.

The concept of pneuma as the material substance of life, which acts as a vehicle driving all reactions of the body, was formalised by Aristotle (384–322 BC). The pneuma was a sort of ‘air’ substance that was diffusely present in living organisms; the mind was pneuma and had no specific localisation. According to Aristotle, the pneuma originated from the heart, and the heart was considered to be the primary organ controlling production of pneuma and also the central seat for sensory integration and initiation of movements. The heart was connected to the periphery by vessels and nerves (between which Aristotle made no distinction). The brain, which Aristotle almost certainly dissected, was of a secondary importance. The brain was a cold and bloodless organ; senseless, indifferent to touch, or even to cutting, and disconnected from the body. Most importantly, a brain was absent in many organisms that were able to move and react to the environment. The primary brain function, according to Aristotle, was to cool the pneuma emerging form the heart and thus temper the passions (Aristotle, 1992; Clarke, 1963).