Non-Neuronal Cells of the Nervous System: Function and Dysfunction

1147 Pages·2003·22.308 MB·1-1172\1147

by  Leif Hertz (Eds.)

PREFACE
ADanishfolk-taledescribeshowthe‘wiseMolboer’wantedtohelpatreehangingover
apondtodrinkfromthewaterbybendingitsbranchesdownintothewater.Sinceitwasa
talltreeandtheyhadnoladderandnorope,theyclimbedupinthetree,onemanhanging
onto abranch,the secondto hislegs and soon(Fig. 1).They startedpullinghard,but
suddenlythehandsofthemanclosesttothetreestartedhurtingandhewantedtospitin
themtoalleviatethepain.So,looseninghisgrip,heshoutedtotheothers‘stoppullingfor
awhile,sowedon’tfalldown’,butasillustratedinFig.1,thatdidn’thelp.Thesituationin
thenervoussystemissimilar,nocellorcelltype,whetherneuronalornon-neuronal,can
malfunctionorabandonitsassignedfunctionwithoutseriousconsequencesforothercells
withwhichitinteracts.
Within the last decades we have begun to realize that the cells that populate the
nervous system besides the neurons, and greatly outnumber them, have their specific
and important functions, which cannot be abandoned without serious consequences
for the nervous system as a whole. The present 3 volumes describe these cells, many
of their functions and some of their beneficial or adverse roles in disease. The non-
neuronal cells of the nervous system cells include all inhabitants of brain parenchyma
with the exception of neurons, e.g., astrocytes with their extensive processes and
filopodia (Wolff and Chao; Derouiche) and gap junction-mediated coupling (Scemes
and Spray); myelinating and non-myelinating oligodendrocytes (Szuchet and Seeger);
microglia, which has both cytoprotective or cytotoxic properties (Schwartz; Kalman);
Fig. 1. When one (cell type) loses its grip, they all fall. From: Fausbøll, V., 1862. Beretning om de
VidtbekjendteMolboersViseGerningerogTappreBedrifter,Fr.WøldikesForlagsboghandel,Copenhagen.
vi Preface
choroid plexus epithelial cells, which in spite of their very small number are the main
regulators of CSF composition (Weaver et al.); ependyma cells and other cells lining
the ventricles (Szele and Szuchet), and vascular endothelial cells. Interactions between
transport processes across the endothelial cells and across the astrocytic membrane are
crucial for regulation of ion and fluid distribution in the extracellular space of the
brain (Chen and Spatz). Immune cells, bacteria and virus enter the brain via
endothelial cells or via the choroid plexus (Couraud et al.). Recently evidence has
been obtained that extraparenchymal macrophages and meningeal cells also are
important players both during normal brain function and following injury (Mercier
and Hatton; Kalman; Dezawa).
Functional interactions between neurons and non-neuronal cells have been especially
wellstudiedinthehypothalamic-hypophysealsystems(Salmetal.;MercierandHatton;
Melcangi et al.) and recently it has been established that endothelial cells and tanycytes
alsopartakeintheseinteractions(Pre´votetal.).Ithaslongbeenknownthatneuronsand
astrocytesinteractcloselyduringdevelopment,butonlyduringthelastcoupleofyearshas
informationbeenobtainedabouttheroleofradialglialcellsasmultipotentialstemcells,
bothinthebrain(GomesandRehen;SzeleandSzuchet)andtheretina(Bringmannetal.),
and about interactions between glial cells (astrocytes and Mu¨ller cells) and endothelial
cells during retinal development (Stone and Valter). Regulation of astrocytic cell cycle
progressionisessentialfornormaldevelopment,anddysregulationmayleadtomalignant
transformationofglialcells(NakatsujiandMiller).Considerableregenerationofcentral
neurons after trauma has recently been obtained (Dezawa; Schwartz), although this
problem is still not solved (Kalman). Enteric glial cells regulate mucosal and vascular
integrity,andmaybedirectlyinvolvedininflammatoryandpermeabilitydisordersofthe
gastrointestinaltract(Savidgeetal.).
Astrocytes account for a sizeable fraction of oxidative metabolism in the brain
(Gruetter; Hertz, Peng et al.) and both neurons and astrocytes metabolize glucose by
glycolysisaswellasoxidativemetabolism(RobertsandChih).Astrocytesareessentialfor
supplying glutamatergic neurons with precursors for transmitter glutamate and
GABAergic neurons with precursors for GABA (Schousboe and Waagepetersen). They
producecholesterolandgeneratehigh-densitylipoproteinwithapolipoproteins,whichare
crucialforcholesteroltransportbetweenbraincells(ItoandYokoyama).Theyexpressa
high density of a ‘peripheral-type’ benzodiazepine receptor, which mediates cholesterol
transport from the outer to the inner mitochondrial membrane (Be´langer et al).
Cholesterolisusedinbothneuronsandastrocytesforsynthesisofmembraneconstituents
(Ito and Yokoyama) and especially in astrocytes and Schwann cells for formation of
neurosteroids,whichexertneuromodulatoryand neurotrophicactions (Melcangietal.).
Astrocytes express a multitude of ionotropic and metabotropic receptors, which affect
astrocytic activities and thereby CNS function (Hansson and Ro¨nnba¨ck). They also
expressneurotrophicfactorsandcytokinesandtheirreceptors(NakagawaandSchwartz),
anda‘transactivation’processcantakeplaceinwhichstimulationofaGprotein-coupled
receptorleadsto‘shedding’ofagrowthfactor,whichinturnstimulatesareceptorprotein
tyrosinekinasebyanautocrine/paracrineeffect(Peng).Bothneuronsandastroglialcells
express all the molecular components required for NO-cGMP-PKG signaling, and
astrocytescanproducelargeamountsofNObystimulationoftheinducibleNOsynthase
(GarciaandBaltrons).
Preface vii
Transmitter effects release Ca2+ bound to intracellular stores of different types
(Scapagninietal.;HanssonandRo¨nnba¨ck).NeuronallyreleasedglutamatetriggersCa2+
wavesthroughtheastrocyticsyncytium,whichinturnmaystimulateclosebyneuronsby
astrocyticreleaseofglutamate,modulatingneuronalsignaltransmission(Cornell-Bellet
al.;Shuai etal.). Amultitude oftransportersand metabolicproduction ofCO regulate
2
pHinastrocytesandinCSFandbrainextracellularfluid(McAlearandBevensee;Weaver
etal.).AfterincreasesinextracellularKþconcentrationbyreleaseofKþfromstimulated
neurons,excessKþisremovedfromtheextracellularspacebyastrocytes,mainlybyactive
uptakemechanisms(Walz).However,gapjunctioncouplingcombinedwithselective,high
Kþ conductance sets the stage for a passive spatial buffering mechanism, which can
redistribute locally elevated Kþ concentrations across short distances, e.g., in the retina
(Bringmann et al.; Scemes and Spray), and in the toad and fish brain, where they
contributetomodulationofneuronalactivityandtherebybehaviour(Laming).
Given these important functions of non-neuronal cells in the nervous system it is
exceedinglydifficultinmostofitsdiseasestoestablishwhetherneuronsoroneofthenon-
neuronalcelltypesweretheonesthatinitially‘looseneditsgrip’.However,recentlyithas
been shown beyond doubt that Alexander disease is a primary disorder of astrocytes,
caused by mutations in the GFAP gene (Eng and Lee). Hepatic encephalopathy is
characterizedbyamultitudeofeffectsonastrocytes,manyofwhichmaybesecondaryto
ammonia toxicity (Be´langer et al.). Astrocytic reactions, combined with microglial
activation, also play essential roles in the pathogenesis of HIV-associated dementia
(Kovacs et al.; Ghorpade and Gendelman), Prion disease (Brown and Sassoon), and
chronic pain (Raghavendra and DeLeo). Proinflammatory cytokines and/or glutamate
excitotoxicity are becoming recognized as major pathogenetic factors not only in these
conditions,butalsoinMS(Werneretal.),ischemicbraindisease(Ha˚bergandSonnewald;
Schousboe and Waagepetersen), and Alzheimer’s disease (Barger), and may become
targetsoftherapeuticintervention.Thereasonsforglutamateexcitotoxicityaremany,and
include enhanced release from neurons, astrocytes or microglia, compromised uptake,
increased synthesis or decreased degradation in astrocytes or oligodendrocytes and
heightenedsensitivityofglutamatereceptors.DepolarizationofretinalMullercellsdueto
a decreased Kþ conductance in retinopathies contributes to glutamate toxicity by
impairinguptakeofglutamateinconjunctionwithNaþ(Bringmannetal.).
It is disputed whether astrocytes and microglia carry out a neuroprotective role in
Parkinson’s disease or mediate deleterious events related to the production of pro-
oxidantandpro-inflammatorycompounds(PrzedborskiandGoldman).Similarly,heme
oxygenase-1 (HO-1), which is upregulated after ischemic and other insults as well as in
Alzheimer’s disease may either be cytoprotective or neuroendangering (Schipper).
Astrocytes resist anoxia better than oligodendrocytes (Marrif and Juurlink). Oxidative
stress, polyol pathway flux, increased advanced glycosylation end product formation
and deficient neurotrophic support compromise Schwann cells and the axons they
ensheath during diabetic neuropathy (Mizisin). Glial dysfunction appears also to be
linked to psychiatric illness, as indicated by a glial cells loss in specific regions of the
human brain in depressive disorders (Price) and by the observation that all three
conventional antibipolar drugs at therapeutically relevant concentrations exert similar
effects on signaling-related parameters in cultured astrocytes (Hertz, Chen et al.). An
imbalance between the type-1/type-2 immune systems with preponderance of the type-2
viii Preface
immune response in schizophrenia may reflect differential activation of astrocytes and
microglial cells (Mu¨ller and Schwarz).
The description in these three volumes of the complex functions of non-neuronal
cells in the nervous system and their interactions with each other and with neurons
under normal and pathological conditions will hopefully help in establishing an
integrated perception of nervous system function and eventually in the development of
rational therapy against many diseases where we now are relatively helpless. This
endeavour has been made possible by the dedicated efforts of the authors of each of
the 51 chapters. I, as the editor, owe my deepest gratitude to each individual author
and thank all authors for contributing their profound knowledge, for their patience
with me and for their open-mindedness. I would also like to express my thanks to
Alden Books, and especially to Dr. Carol Cooper, for her great helpfulness and
effectiveness, to the Series Editor, Dr. E.E. Bittar for encouraging me to produce these
volumes and to Ms. Joan Anuels and Mr. Hendrik van Leusen of Elsevier for
continued support.
LEIFHERTZ
DickeyLake,August2nd,2003.
TABLEOFCONTENTS
Preface ..................................................................... v
Volume I
Structure,Organization, Development and Regeneration
Chapter1
Cytoarchitectonicsofnon-neuronalcellsinthecentralnervoussystem .................. 1
JoachimR.WolffandT.IvoChao
Chapter2
Oligodendrocytephenotypicalandmorphologicalheterogeneity:
areexaminationofoldconceptsinviewofnewfindings ................................ 53
SaraSzuchetandMarkA.Seeger
Chapter3
Regulationofcellcycleprogressioninastrocytes ...................................... 75
YujiNakatsujiandRobertH.Miller
Chapter4
Roleofneuron–gliainteractionsinnervoussystemdevelopment:highlights
onradialgliaandastrocytes .......................................................... 97
Fla´viaCarvalhoAlcantaraGomesandStevensKastrupRehen
Chapter5
Cellsliningtheventricularsystem:evolvingconceptsunderlying
developmentaleventsintheembryoandadult ....................................... 127
FrancisG.SzeleandSaraSzuchet
Chapter6
Theperisynapticastrocyteprocessasaglialcompartment-immunolabeling
forglutaminesynthetaseandotherglialmarkers .................................... 147
A.Derouiche
Chapter7
Theastrocyticsyncytium ............................................................ 165
ElianaScemesandDavidC.Spray
Chapter8
Structuralplasticityofnonneuronalcellsinthehypothalamo-
neurohypophysealsystem:intherightplaceattherighttime ........................ 181
A.K.Salm,A.E.AyoubandB.E.Lally
Chapter9
Glial–neuronal–endothelialinteractionsandtheneuroendocrine
controlofGnRHsecretion .......................................................... 199
VincentPrevot,SandrineDeSerannoandCeciliaEstrella
x Contents
Chapter10
MeningesandperivasculatureasmediatorsofCNSplasticity ........................ 215
FredericMercierandGlennI.Hatton
Chapter11
Mechanismsofinfiltrationofimmunecells,bacteriaandviruses
throughbrainendothelium .......................................................... 255
P.O.Couraud,X.NassifandS.Bourdoulous
Chapter12
Hydrocephalusdisorders:theirbiophysicalandneuroendocrine
impactonthechoroidplexusepithelium ............................................. 269
CharlesE.Weaver,PaulN.McMillan,JohnA.Duncan,
EdwardG.StopaandConradE.Johanson
Chapter13
Rolesofretinalmacrogliainmaintainingthestabilityoftheretina .................. 295
JonathanStoneandKrisztinaValter
Chapter14
Functionanddysfunctionofentericglia ............................................. 315
TorC.Savidge,JulieCabarrocasandRolandS.Liblau
Chapter15
SchwanncellinteractionswithaxonsandCNSglialcellsduring
opticnerveregeneration ............................................................ 329
MariDezawa
Chapter16
Controlofmicroglialactivitybyprotectiveautoimmunity ........................... 347
MichalSchwartz
PartI:ColourPlates ................................................................ 367
TABLEOFCONTENTS
Volume II
Biochemistry, Physiology and Pharmacology
Chapter17
Aroleforlactatereleasedfromastrocytesinenergyproduction
duringneuralactivity? .............................................................. 391
EugeneL.RobertsJr.andChing-PingChih
Chapter18
Principlesofthemeasurementofneuro-glialmetabolismusinginvivo
13CNMRspectroscopy .............................................................. 409
RolfGruetter
Chapter19
Ion,transmitteranddrugeffectsonenergymetabolisminastrocytes ................. 435
LeifHertz,LiangPeng,ChristelC.Kjeldsen,
BronaS.O’DowdandGeraldA.Dienel
Chapter20
RoleofastrocytesinhomeostasisofglutamateandGABAduringphysiological
andpathophysiologicalconditions ................................................... 461
ArneSchousboeandHelleS.Waagepetersen
Chapter21
Astrocyticreceptorsandsecondmessengersystems .................................. 475
ElisabethHanssonandLarsRo¨nnba¨ck
Chapter22
Transactivationinastrocytesasanovelmechanismofneuroprotection ............... 503
LiangPeng
Chapter23
Rolesofgliacellsincholesterolhomeostasisinthebrain ............................. 519
Jin-ichiItoandShinjiYokoyama
Chapter24
Non-neuronalcellsinthenervoussystem:sourcesandtargets
ofneuroactivesteroids .............................................................. 535
RobertoC.Melcangi,In˜igoAzcoitia,MariaritaGalbiati,
ValerioMagnaghi,DanielGarcia-OvejeroandLuisM.Garcia-Segura
Chapter25
Expressionofneurotrophicfactorsandcytokinesandtheirreceptorson
astrocytesinvivo ................................................................... 561
TakaoNakagawaandJoanP.Schwartz
vi Contents
Chapter26
Thenitricoxide/cyclicGMPpathwayinCNSglialcells .............................. 575
AgustinaGarc´ıaandMar´ıaAntoniaBaltrons
Chapter27
Potassiumhomeostasisinthebrainattheorganandcelllevel ....................... 595
WolfgangWalz
Chapter28
Potassiumandglia-derivedslowpotentialshiftsinrelationtobehaviour ............. 611
PeterR.Laming
Chapter29
RegulationofCa2þstoresinglialcells ............................................... 635
GiovanniScapagnini,ThomasJ.NelsonandDanielL.Alkon
Chapter30
Decodingcalciumwavesignaling .................................................... 661
A.H.Cornell-Bell,P.JungandV.Trinkaus-Randall
Chapter31
Mathematicalmodelingofintracellularandintercellularcalciumsignaling ........... 689
Jian-WeiShuai,SuhitaNadkarni,PeterJung,AnnCornell-Bell
andVickeryTrinkaus-Randall
Chapter32
pHregulationinnon-neuronalbraincellsandinterstitialfluid ....................... 707
SuzanneD.McAlearandMarkO.Bevensee
Chapter33
AVPeffectsandwaterchannelsinnon-neuronalCNScells .......................... 747
YeChenandMariaSpatz
TABLEOFCONTENTS
VolumeIII
PathologicalConditions
Chapter34
Alexanderdisease:aprimarydiseaseofastrocytes ................................... 773
LawrenceF.EngandYuenLingLee
Chapter35
Glialreactionandreactiveglia ...................................................... 787
M.Ka´lma´n
Chapter36
Contributionsofastrocytestoischemia-inducedneuronal
dysfunctioninvivo .................................................................. 837
AstaHa˚bergandUrsulaSonnewald
Chapter37
Differentialvulnerabilityofoligodendrocytesandastrocytes
tohypoxic–ischemicstresses ........................................................ 857
HusniaMarrifandBernhardH.J.Juurlink
Chapter38
Glialhemeoxygenase-1inCNSinjuryanddisease ................................... 869
HymanM.Schipper
Chapter39
AstrocytesandmicrogliainAlzheimer’sdisease ..................................... 883
StevenW.Barger
Chapter40
Non-neuronalinteractionsinHIV-1-associateddementia ............................. 901
AnujaGhorpadeandHowardE.Gendelman
Chapter41
Glycoproteingp120-mediatedastrocyticdysfunction ................................. 921
EvaZ.Kovacs,BeverlyA.BushandDaleJ.Benos
Chapter42
Theroleofastrocytesandmicrogliainpersistentpain ............................... 951
VasudevaRaghavendraandJoyceA.DeLeo
Chapter43
PathogenicroleofglialcellsinParkinson’sdisease .................................. 967
S.PrzedborskiandJamesE.Goldman
Chapter44
Upregulationofperipheral-type(mitochondrial)benzodiazepinereceptors
inhyperammonemicsyndromes:consequencesforneuronalexcitability .............. 983
MireilleBe´langer,SamirAhboucha,PaulDesjardinsandRogerF.Butterworth
vi Contents
Chapter45
Roleofthecytokinenetworkinmajorpsychoses .................................... 999
NorbertMu¨llerandMarkusJ.Schwarz
Chapter46
Sharedeffectsofallthreeconventionalanti-bipolardrugsonthe
phosphoinositidesysteminastrocytes ............................................... 1033
LeifHertz,YeChen,YulyBersudskyandMarinaWolfson
Chapter47
Gliallossinmooddisordersandschizophrenia ..................................... 1049
JosephL.Price
Chapter48
Glutamateexcitotoxicityintheimmunopathogenesisofmultiplesclerosis ........... 1059
P.Werner,E.Brand-SchieberandC.S.Raine
Chapter49
Roleofgliainpriondisease ........................................................ 1085
DavidR.BrownandJudythSassoon
Chapter50
Schwanncellsindiabeticneuropathy ............................................... 1105
AndrewP.Mizisin
Chapter51
Mu¨llercellsinretinopathies ........................................................ 1117
A.Bringmann,M.FranckeandA.Reichenbach
PartIII:ColourPlates ............................................................. 1133
Index .............................................................................. 1145