Frontal-subcortical protein expression following prenatal exposure to maternal inflammation

• Published in: PloS one Vol. 6; no. 2; p. e16638
• Main Authors: Deng, Michelle Y, Lam, Sylvia, Meyer, Urs, Feldon, Joram, Li, Qi, Wei, Ran, Luk, Lawrence, Chua, Siew Eng, Sham, Pak, Wang, Yu, McAlonan, Grainne Mary
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.02.2011; Public Library of Science (PLoS)
• Subjects: 14-3-3 protein; Animals; Autism; Autoimmune diseases; Biology; Biomarkers; Blotting, Western; Brain; Cortex (frontal); Cortex (olfactory); Creatine; Creatine kinase; Dehydrogenase; Discriminant analysis; Disruption; Female; Gel electrophoresis; Gene expression; Genetic research; Gestation; Guanine; Heat shock proteins; Homeostasis; Immune response; Immune system; Inflammation; Inflammation - immunology; L-Lactate dehydrogenase; Laboratories; Lactate dehydrogenase; Lactic acid; MAP kinase; Mass spectrometry; Mass spectroscopy; Medicine; Mental disorders; Mice; Mice, Inbred C57BL; Mitogens; Mothers; Multivariate Analysis; NADH; Neostriatum; Neostriatum - drug effects; Neostriatum - immunology; Neostriatum - metabolism; Neurobiology; Neurodevelopmental disorders; Neurosciences; Nicotinamide adenine dinucleotide; Oxidation; Oxidative stress; Poly I-C - pharmacology; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - immunology; Prefrontal Cortex - metabolism; Pregnancy; Pregnant women; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - immunology; Prenatal Exposure Delayed Effects - metabolism; Protein binding; Protein expression; Protein kinase; Protein kinases; Proteins; Proteomes; Proteomics; Psychiatry; Reproducibility of Results; Risk factors; Rodents; Schizophrenia; Signal transduction; Signaling; Studies; Transcriptome - drug effects; Transcriptome - immunology; Two-Dimensional Difference Gel Electrophoresis; Hong Kong China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0016638

Maternal 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.