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dc.contributor.authorPhillips, Tom J
dc.contributor.authorScott, Hannah
dc.contributor.authorMenassa, David A
dc.contributor.authorBignell, Ashleigh L
dc.contributor.authorSood, Aman
dc.contributor.authorMorton, Jude S
dc.contributor.authorAkagi, Takami
dc.contributor.authorAzuma, Koki
dc.contributor.authorRogers, Mark F
dc.contributor.authorGilmore, Catherine E
dc.contributor.authorInman, Gareth J
dc.contributor.authorGrant, Simon
dc.contributor.authorChung, Yealin
dc.contributor.authorAljunaidy, Mais M
dc.contributor.authorCooke, Christy-Lynn
dc.contributor.authorSteinkraus, Bruno R
dc.contributor.authorPocklington, Andrew
dc.contributor.authorLogan, Angela
dc.contributor.authorCollett, Gavin P
dc.contributor.authorKemp, Helena
dc.contributor.authorHolmans, Peter A
dc.contributor.authorMurphy, Michael P
dc.contributor.authorFulga, Tudor A
dc.contributor.authorConey, Andrew M
dc.contributor.authorAkashi, Mitsuru
dc.contributor.authorDavidge, Sandra T
dc.contributor.authorCase, C Patrick
dc.date.accessioned2018-06-18T15:48:27Z
dc.date.available2018-06-18T15:48:27Z
dc.date.issued2017-08-22
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277188
dc.description.abstractSome neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBrain
dc.subjectFetus
dc.subjectPlacenta
dc.subjectAnimals
dc.subjectRats
dc.subjectPregnancy Complications
dc.subjectReactive Oxygen Species
dc.subjectAntioxidants
dc.subjectMicroscopy, Confocal
dc.subjectGene Expression
dc.subjectOxidative Stress
dc.subjectFetal Development
dc.subjectOrganogenesis
dc.subjectPregnancy
dc.subjectFemale
dc.subjectBiomarkers
dc.subjectHypoxia
dc.titleTreating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2017
prism.publicationNameSci Rep
prism.startingPage9079
prism.volume7
dc.identifier.doi10.17863/CAM.24481
dcterms.dateAccepted2017-06-09
rioxxterms.versionofrecord10.1038/s41598-017-06300-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-08-22
dc.contributor.orcidScott, Hannah [0000-0002-2497-549X]
dc.contributor.orcidPocklington, Andrew [0000-0002-2137-0452]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_00015/3)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)
pubs.funder-project-idMedical Research Council (MC_U105663142)
cam.issuedOnline2017-08-22


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International