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Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease

Scott, Hannah, Phillips, Thomas, Stuart, Greer C., Rogers, Mark F., Steinkraus, Bruno R., Grant, Simon R. and Case, C. Patrick 2018. Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease. Neuronal Signaling 2 (4) , NS20180139. 10.1042/NS20180139

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Abstract

Prenatal development is a critical period for programming of neurological disease. Preeclampsia, a pregnancy complication involving oxidative stress in the placenta, has been associated with long-term health implications for the child, including an increased risk of developing schizophrenia and autism spectrum disorders in later life. 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 γ-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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Portland Press
ISSN: 2059-6553
Date of First Compliant Deposit: 18 September 2018
Date of Acceptance: 18 September 2018
Last Modified: 28 Jun 2019 02:29
URI: http://orca.cf.ac.uk/id/eprint/115072

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