title: Frontal-subcortical protein expression following prenatal exposure to maternal inflammation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Michelle Y
authors.initials: MY
authors.lastname: Deng
authors.forename: Sylvia
authors.initials: S
authors.lastname: Lam
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
authors.forename: Joram
authors.initials: J
authors.lastname: Feldon
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Ran
authors.initials: R
authors.lastname: Wei
authors.forename: Lawrence
authors.initials: L
authors.lastname: Luk
authors.forename: Siew Eng
authors.initials: SE
authors.lastname: Chua
authors.forename: Pak
authors.initials: P
authors.lastname: Sham
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Grainne Mary
authors.initials: GM
authors.lastname: McAlonan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009035:Mothers; D015999:Multivariate Analysis; D017072:Neostriatum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D040901:Proteomics; D015203:Reproducibility of Results; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology*; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D011070:Poly I-C