Prenatal and Postnatal Determinants of Development

368 Pages·2016·7.917 MB·English

by  David W. Walker (eds.)

Neuromethods 109
David W. Walker Editor
Prenatal and
Postnatal
Determinants
of Development
N
EUROMETHODS
SeriesEditor
Wolfgang Walz
University ofSaskatchewan,
Saskatoon, SK,Canada
Forfurther volumes:
http://www.springer.com/series/7657
.
Prenatal and Postnatal
Determinants of Development
Edited by
David W. Walker
The Ritchie Centre,
Hudson Institute of Medical Research, Monash Medical Centre
&
Department of Obstetrics & Gynaecology,
Monash University - Clayton Campus
Melbourne, Australia
Editor
DavidW.Walker
TheRitchieCentre
HudsonInstituteofMedicalResearch
MonashMedicalCentre
&
DepartmentofObstetrics&Gynaecology
MonashUniversity-ClaytonCampus
Melbourne,Australia
ISSN0893-2336 ISSN1940-6045 (electronic)
Neuromethods
ISBN978-1-4939-3013-5 ISBN978-1-4939-3014-2 (eBook)
DOI10.1007/978-1-4939-3014-2
LibraryofCongressControlNumber:2015955169
SpringerNewYorkHeidelbergDordrechtLondon
©SpringerScience+BusinessMediaNewYork2016
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Series Preface
Experimental life sciences have two basic foundations: concepts and tools. The Neuro-
methodsseriesfocusesonthetoolsandtechniquesuniquetotheinvestigationofthenervous
system and excitable cells. It will not, however, shortchange the concept side of things as
carehasbeentakentointegratethesetoolswithinthecontextoftheconceptsandquestions
underinvestigation.Inthisway,theseriesisuniqueinthatitnotonlycollectsprotocolsbut
also includes theoretical background information and critiques which led to the methods
andtheirdevelopment.Thusitgivesthereaderabetter understandingoftheoriginofthe
techniquesandtheirpotentialfuturedevelopment.TheNeuromethodspublishingprogram
strikes a balance between recent and exciting developments like those concerning new
animal models of disease, imaging, in vivo methods, and more established techniques,
including, for example, immunocytochemistry and electrophysiological technologies. New
traineesinneurosciencesstillneedasoundfootingintheseoldermethodsinordertoapply
acriticalapproachtotheir results.
Under the guidance of its founders, Alan Boulton and Glen Baker, the Neuromethods
serieshasbeenasuccesssinceitsfirstvolumepublishedthroughHumanaPressin1985.The
seriescontinuestoflourishthroughmanychangesovertheyears.Itisnowpublishedunder
theumbrellaofSpringerProtocols.Whilemethodsinvolvingbrainresearchhavechangeda
lot since theseriesstarted, thepublishingenvironmentand technologyhavechanged even
more radically. Neuromethods has the distinct layout and style of the Springer Protocols
program,designedspecificallyfor readabilityandeaseofreferenceinalaboratorysetting.
Thecarefulapplicationofmethodsispotentiallythemostimportantstepintheprocess
of scientific inquiry. In the past, new methodologies led the way in developing new dis-
ciplines in the biological and medical sciences. For example, Physiology emerged out of
Anatomyinthenineteenthcenturybyharnessingnewmethodsbasedonthenewlydiscov-
eredphenomenonofelectricity.Nowadays,therelationshipsbetweendisciplinesandmeth-
ods are more complex. Methods are now widely shared between disciplines and research
areas. New developments in electronic publishing make it possible for scientists that
encounter new methods to quickly find sources of information electronically. The design
of individual volumes and chapters in this series takes this new access technology into
account. Springer Protocols makes it possible to download single protocols separately. In
addition, Springer makes its print-on-demand technology available globally. A print copy
canthereforebeacquiredquicklyandforacompetitivepriceanywhereintheworld.
Saskatoon,Saskatchewan,Canada WolfgangWalz
v
.
Preface
Theepidemiologicalandexperimentalevidencethatstress,illness,ornutritionaldeprivation
during pregnancy will impact on the structural and functional development of the brain is
now compelling. This may cause not only catastrophic damage to the brain at birth, as
shown by brain damage that leads to cerebral palsy, but also more subtle and long-term
effects that manifest as behavioral disorders in the child and adult such as autism, schizo-
phrenia,andcompulsive/addictivebehaviors.Inadditiontotheseextrinsic(environmental)
influences, epigenetic, sex, and parental genomic effects have roles in determining the
outcomesofpregnancyfor theinfantandchild.
The purpose of this book is to provide the reader with an introduction to all the
methods and major approaches now being used to study the structural and functional
development of the brain. This area of research has gained greater prominence in recent
yearsbecausesomanymorepretermbabiessurvive,andtheirbirthcanoccurattimeswhen
major cell migration and phenotypic transitions in the brain are still underway. Because of
this we needed to cover topics such as early anatomical development, the emergence of
function, and the processes that lead to damage and repair of the growing and immature
brain;wehavecoveredabroaderareaofresearchthanwouldcustomarilybeexpected.
The book is divided into three parts—Development, Programming and Stress, and
BrainDamage—CausesandConsequences.
InPart1(Development),PeterKozulin,GonzaloAlmarza,IlanGobius,andLindaJ.
Richardsintroducetheconceptof“inutero”electroporation (IUE)thatprovidesameans
of labeling neural progenitor cells and tracking their progeny in vivo. Using promoter-
specific reporter constructs, and with precise transfection of progenitor subpopulations,
theyshowhowitispossibletoinduceorrepressgeneexpressionofneuronsinaspatiallyand
temporallyspecificmanneratveryearlyembryonicstages.IsabelMartı´nez-Garay,Fernando
Garcı´a-Moreno,NavneetVasistha,AndreMarques-Smith,andZolta´nMolna´ralsoreporton
the use of in utero electroporation to study key aspects of neural development, such as
progenitorproliferation,neurogenesis,clonalandlineageanalysis,neuronalmigration,and
circuit formation in various species from the chick to higher mammals with gyrencephalic
braindevelopment.Thismethodcanbealsousedtomonitorandmodulatetheformationof
cortical circuits in a controlled manner. Then, Hui XuanNg and Joanne M. Britto discuss
how to studytheplacement ofinterneuronsand pyramidal neuronsduring corticogenesis.
Usingtransgenictechnologytofluorescentlylabelandisolateinterneuronprogenitorcells,
theydiscusshowthecellsisolatedfromthemedialgerminalepitheliumcanbetransplanted
inuterointotheembryoniclateralventricle;theyfurtherdiscusshowthismighteventually
becomeacell-basedtherapytorectifyGABAergicdysfunctionintheneocortex.
Techniques for studying the functional development of the infant human brain are
introduced in the chapter by Sampsa Vanhatalo and Peter Fransson. The function of
developing sensory systems can be readily studied using EEG even at a developmental
stage when the sensory connections are only incompletely formed, and they develop the
ideaofderivinglarge-scalemapsof functionalconnectivityfromcontinuousrecordsofthe
EEG and blood deoxygenation (fMRI) of the infant brain, despite the immaturity of
neurovascular coupling making such functional tests a challenge. Flora Wong develops this
theme by discussing the constraints in measuring cerebral blood flow in infants due to the
vii
viii Preface
necessitytousenoninvasivetechniques.Thereisnogeneralagreementonthebestapproach
to measure cerebral blood flow, but despite the methodological differences, all of the
commonly used techniques yield reasonably comparable results in terms of absolute values
andofindicatorsofcerebrovascular reactivity.
Functional development of the brain during fetal life is discussed at length by Dan
Rurak, including the changes of body movements, breathing activity, and cardiovascular
function which together denote the development of fetal sleep-like states. Understanding
these phenomena is important because fetal monitoring in human pregnancy is based on
changes in fetal behavior that is used diagnostically to distinguish abnormal from normal
fetaldevelopment,withimplicationsforcliniciansthatmaydeterminehowthefinalstagesof
pregnancyaremanaged.Finally,for thispart,thebiophysicalandhormonalcuesrelatedto
photoperiod,howtheyaffectfetalbraindevelopment,andwhymaternalchronodisruption
disruptsthefetalcircadiansystemarediscussedbyMariaSero´n-Ferre´,HansG.Richter,and
Claudia Torres-Farfan. The difficulties of finding an experimental animal model that
resembles the human setting of chronodisruption during pregnancy (e.g., shift-work) and
the need to identify changes at the level of the transcriptome, microRNA regulome (miR-
Nome),andproteomearediscussed.
InPart2(ProgrammingandStress),differentexperimentalapproachestoevaluating
the postnatal outcomes of pregnancy where maternal stress has occurred transiently or is
presentchronicallyarecoveredinfivechapters.Thisareaofresearchisreceivingincreasingly
greater prominence due to the recognition that many forms of pathophysiology and ill-
healthinadolescentandadultlifemayhaveoriginsinearlydevelopment,includingfetaland
early postnatal life (viz., Developmental Origins of Health & Adult Disease). Beverley S.
Muhlhausler and Jessica Gugusheff discuss studies in rodent models that demonstrate how
preferenceforparticularfoodscanbeprogrammedbeforebirthandelucidatethebiological
mechanisms that drive these determinant (programming) effects in the mesolimbic reward
pathwayintheoffspring.SarahJ.SpencerandTrishA.Jenkinsprovideadetaileddescription
ofseveralsimplebutelegantprenatal/postnatalanimalmodelsusedtomimictheeffectsof
earlylifeoverfeeding,andtostudytheimpactofthisonbrainandmetabolicdevelopment.
HelenaC.ParkingtonandHaroldA.Colemanpresentmethodsfor theeffectsofmaternal
obesityonoffspringbraindevelopment,andfordelineatingeffectsonspecificbrainregions
and outcomes reflected in behaviours appropriately assessed for gender and the animal
species under study. The placenta is likely to be the crucial interface between the maternal
andfetal“environments,”andHannhaK.Palliser,GreerA.Bennett,MeredithA.Kelleher,
Angela L. Cumberland, David W . Walker, and Jonathan J. Hirst discuss metabolic and
endocrineresponseswithintheplacenta,particularlyinrelationtoprecursorsubstancesthat
enable synthesis of neuroactive neurosteroids in the fetal and newborn brain. A host of
neurodevelopmentalprocessesaremodulatedbyserotonin(5-HT),whichforsomeperiod
of fetal life is largely of maternal and placental origin. Juan C. Velasquez and Alexandre
Bonnin provide details of recently developed methods that can be applied to the study of
how maternal-fetal transfer of therapeutic drugs such as selective serotonin reuptake inhi-
bitors(SSRIs)crosstheplacentaandimpactonthedevelopmentoffetalbraincircuits.They
have shown that dysregulation of placental 5-HT transfer impacts a variety of critical
signalingpathwaysthatcanleadtolong-term effectsonpostnatalbrainfunction.
Humanepidemiologicalstudieshaveindicatedanassociationbetweeninfectionduring
pregnancy and an increased risk of neurodevelopmental disorders such as schizophrenia in
offspring.As infectionsarising fromvariouscauses havea similardebilitating effectinlater
life,itisthoughtthatactivationofthematernalimmuneresponsemaybethecriticalfactor
Preface ix
altering fetal brain development. Udani Ratnayake and Rachel Hill discuss various animal
models of prenatal exposure to infection that result in behavioral abnormalities in the
offspring that are comparable to those seen in schizophrenic patients and argue that such
approaches, particularly viral illness modeled using polyriboinosinic-polyribocytidilic acid
(PolyI:C),provideausefultoolforunderstandingtheneurodevelopmentalbasisofschizo-
phreniaandfor testingtreatmentstrategies.
In Part 3 (Brain Damage: Causes and Consequences), four teams of researchers
address issues that arise from the continued and pressing need to predict, prevent, and
treatperinatalbraininjury—imperativesthathaveincreasedwiththegreatersurvivalratesof
premature infants. Mary Tolcos, David H. Rowitch, and Justin Dean discuss approaches to
identifying causes of white matter injury, which they argue is due in part to impaired
oligodendrocyte maturation, and which is not always replicated in experimental animal
models of perinatal white matter injury. They propose that adopting a more standard
approach to defining white matter injury is important for validating experimental findings
against the bona fide human condition. Stephen A. Back and A. Roger Hohimer present
evidence obtained from their extensive use of the preterm sheep fetus, chosen because
cerebral development at this time shares many anatomical and physiological similarities
with the preterm human infant. The experimental access to the fetus, made possible with
suchstudiesinpregnantsheep,hasallowedthemtodefinesomeofthecellularandvascular
factorsthatcontributetopretermwhiteandgraymatterinjuryandtouseclinicallyrelevant
technologiesofneuroimagingandcerebralbloodflowmeasurementsthatarenotfeasiblein
smaller laboratory animals. Likewise, Lotte G. van den Heuij, Guido Wassink, Alistair Jan
Gunn, and Laura Bennet describe their work with chronically instrumented preterm fetal
sheep that is delineating the key factors that determine the pattern and severity of brain
injury, and discuss how this might determine when and how injury to the immature brain
shouldbetreated.
Finally, neonatal seizure remains a major clinical problem worldwide and current anti-
seizure drugs have limited efficacy and are potentially harmful to the developing brain,
highlighting the need for new experimental approaches in this important area of neonatal
medicine. S. Tracey Bjorkman describes a clinically relevant model of hypoxia/ischemia-
inducedseizuresintheneonatalpigandagainshowshowsuchanapproachmayleadtonew
studiesofseizuresuppressioninthenewborninfant.
Melbourne,Australia DavidW.Walker