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1932-6203622011Feb10PloS onePLoS OneFrontal-subcortical protein expression following prenatal exposure to maternal inflammation.e16638e16638e1663810.1371/journal.pone.0016638Maternal immune activation (MIA) during prenatal life is a risk factor for neurodevelopmental disorders including schizophrenia and autism. Such conditions are associated with alterations in fronto-subcortical circuits, but their molecular basis is far from clear.Using two-dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry, with targeted western blot analyses for confirmation, we investigated the impact of MIA on the prefrontal and striatal proteome from an established MIA mouse model generated in C57B6 mice, by administering the viral analogue PolyI:C or saline vehicle (control) intravenously on gestation day (GD) 9. In striatum, 11 proteins were up-regulated and 4 proteins were down-regulated in the PolyI:C mice, while 10 proteins were up-regulated and 7 proteins down-regulated in prefrontal cortex (PFC). These were proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway, oxidation and auto-immune targets, including dual specificity mitogen-activated protein kinase kinase 1 (MEK), eukaryotic initiation factor (eIF) 4A-II, creatine kinase (CK)-B, L-lactate dehydrogenase (LDH)-B, WD repeat-containing protein and NADH dehydrogenase in the striatum; and guanine nucleotide-binding protein (G-protein), 14-3-3 protein, alpha-enolase, olfactory maker protein and heat shock proteins (HSP) 60, and 90-beta in the PFC.This data fits with emerging evidence for disruption of critical converging intracellular pathways involving MAPK pathways in neurodevelopmental conditions and it shows considerable overlap with protein pathways identified by genetic modeling and clinical post-mortem studies. This has implications for understanding causality and may offer potential biomarkers and novel treatment targets for neurodevelopmental conditions.DengMichelle YMYDepartment of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.LamSylviaSMeyerUrsUFeldonJoramJLiQiQWeiRanRLukLawrenceLChuaSiew EngSEShamPakPWangYuYMcAlonanGrainne MaryGMengJournal ArticleResearch Support, Non-U.S. Gov't20110210
United StatesPLoS One1012850811932-6203O84C90HH2LPoly I-CIMAnimalsBlotting, WesternFemaleInflammationimmunologyMiceMice, Inbred C57BLMothersMultivariate AnalysisNeostriatumdrug effectsimmunologymetabolismPoly I-CpharmacologyPrefrontal Cortexdrug effectsimmunologymetabolismPregnancyPrenatal Exposure Delayed Effectschemically inducedimmunologymetabolismProteomicsReproducibility of ResultsTranscriptomedrug effectsimmunologyTwo-Dimensional Difference Gel ElectrophoresisCompeting Interests: The authors have declared that no competing interests exist.
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