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To investigate if molecules released by the placenta may be important mediators in foetal programming of the brain, we analysed if placental tissue delivered from patients with preeclampsia secreted molecules that could affect cortical cells in culture. Application of culture medium conditioned by preeclamptic placentae to mixed cortical cultures caused changes in neurons and astrocytes that were related to key changes observed in brains of patients with schizophrenia and autism, including effects on dendrite lengths, astrocyte number as well as on levels of glutamate and \u03b3-aminobutyric acid receptors. Treatment of the placental explants with an antioxidant prevented neuronal abnormalities. Furthermore, we identified that bidirectional communication between neurons and astrocytes, potentially via glutamate, is required to produce the effects of preeclamptic placenta medium on cortical cells. Analysis of possible signalling molecules in the placenta-conditioned medium showed that the secretion profile of extracellular microRNAs, small post-transcriptional regulators, was altered in preeclampsia and partially rescued by antioxidant treatment of the placental explants. Predicted targets of these differentially abundant microRNAs were linked to neurodevelopment and the placenta. The present study provides further evidence that the diseased placenta may release factors that damage cortical cells and suggests the possibility of targeted antioxidant treatment of the placenta to prevent neurodevelopmental disorders.<\/jats:p>","DOI":"10.1042\/ns20180139","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T07:55:16Z","timestamp":1538380516000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease"],"prefix":"10.1042","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-549X","authenticated-orcid":false,"given":"Hannah","family":"Scott","sequence":"first","affiliation":[{"name":"School of Clinical Sciences, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, U.K."},{"name":"UK Dementia Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00a0J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, U.K."},{"name":"UK Dementia Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greer\u00a0C.","family":"Stuart","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Southmead Hospital, Bristol BS10 5NB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00a0F.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Intelligent Systems Laboratory, University of Bristol, Merchant Venturers Building, Woodland Road, Bristol BS8 1UB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno\u00a0R.","family":"Steinkraus","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Southmead Hospital, Bristol BS10 5NB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.\u00a0Patrick","family":"Case","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,10,12]]},"reference":[{"key":"2021111608021318200_B1","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.cppeds.2011.01.001","article-title":"Fetal origins of adult disease","volume":"41","author":"Calkins","year":"2011","journal-title":"Curr. 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