PMID- 22681877
OWN - NLM
STAT- MEDLINE
DCOM- 20130621
LR  - 20211203
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 5
DP  - 2012 Jun 9
TI  - Prenatal activation of Toll-like receptors-3 by administration of the viral 
      mimetic poly(I:C) changes synaptic proteins, N-methyl-D-aspartate receptors and 
      neurogenesis markers in offspring.
PG  - 22
LID - 10.1186/1756-6606-5-22 [doi]
AB  - BACKGROUND: There is mounting evidence for a neurodevelopmental basis for 
      disorders such as autism and schizophrenia, in which prenatal or early postnatal 
      events may influence brain development and predispose the young to develop these 
      and related disorders. We have now investigated the effect of a prenatal immune 
      challenge on brain development in the offspring. Pregnant rats were treated with 
      the double-stranded RNA polyinosinic:polycytidylic acid (poly(I:C); 10 mg/kg) 
      which mimics immune activation occurring after activation of Toll-like 
      receptors-3 (TLR3) by viral infection. Injections were made in late gestation 
      (embryonic days E14, E16 and E18), after which parturition proceeded naturally 
      and the young were allowed to develop up to the time of weaning at postnatal day 
      21 (P21). The brains of these animals were then removed to assess the expression 
      of 13 different neurodevelopmental molecules by immunoblotting. RESULTS: 
      Measurement of cytokine levels in the maternal blood 5 hours after an injection 
      of poly(I:C) showed significantly increased levels of monocyte chemoattractant 
      protein-1 (MCP-1), confirming immune activation. In the P21 offspring, 
      significant changes were detected in the expression of GluN1 subunits of NMDA 
      receptors, with no difference in GluN2A or GluN2B subunits or the postsynaptic 
      density protein PSD-95 and no change in the levels of the related small GTPases 
      RhoA or RhoB, or the NMDA receptor modulator EphA4. Among presynaptic molecules, 
      a significant increase in Vesicle Associated Membrane Protein-1 (VAMP-1; 
      synaptobrevin) was seen, with no change in synaptophysin or synaptotagmin. 
      Proliferating Cell Nuclear Antigen (PCNA), as well as the neurogenesis marker 
      doublecortin were unchanged, although Sox-2 levels were increased, suggesting 
      possible changes in the rate of new cell differentiation. CONCLUSIONS: The 
      results reveal the induction by prenatal poly(I:C) of selective molecular changes 
      in the brains of P21 offspring, affecting primarily molecules associated with 
      neuronal development and synaptic transmission. These changes may contribute to 
      the behavioural abnormalities that have been reported in adult animals after 
      exposure to poly(I:C) and which resemble symptoms seen in schizophrenia and 
      related disorders.
FAU - Forrest, Caroline M
AU  - Forrest CM
AD  - Institute for Neuroscience and Psychology, University of Glasgow, West Medical 
      Building, Glasgow, G12 8QQ, UK.
FAU - Khalil, Omari S
AU  - Khalil OS
FAU - Pisar, Mazura
AU  - Pisar M
FAU - Smith, Robert A
AU  - Smith RA
FAU - Darlington, Lynda Gail
AU  - Darlington LG
FAU - Stone, Trevor W
AU  - Stone TW
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120609
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Dcx protein, rat)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (TLR3 protein, rat)
RN  - 0 (Toll-Like Receptor 3)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Biomarkers/metabolism
MH  - Cytokines/metabolism
MH  - Doublecortin Protein
MH  - Female
MH  - Male
MH  - Neurogenesis/*drug effects
MH  - Neurons/metabolism
MH  - Poly I-C/*pharmacology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synapses/drug effects/*metabolism
MH  - Toll-Like Receptor 3/*metabolism
MH  - Viruses/*metabolism
MH  - rho GTP-Binding Proteins/metabolism
PMC - PMC3496691
EDAT- 2012/06/12 06:00
MHDA- 2013/06/26 06:00
PMCR- 2012/06/09
CRDT- 2012/06/12 06:00
PHST- 2012/03/20 00:00 [received]
PHST- 2012/04/25 00:00 [accepted]
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
PHST- 2012/06/09 00:00 [pmc-release]
AID - 1756-6606-5-22 [pii]
AID - 10.1186/1756-6606-5-22 [doi]
PST - epublish
SO  - Mol Brain. 2012 Jun 9;5:22. doi: 10.1186/1756-6606-5-22.