Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection.
Human studies of unexplained cerebral palsy (CP) suggest an association with maternal infection. We used an established model of maternal infection, lipopolysaccharide (LPS) administration, to investigate the molecular changes in the fetal brain that may link maternal infection and CP. We compared gene expression in brains from mouse pups exposed to LPS in utero to those from saline-treated controls. Dams were injected with 50 microg LPS or saline on E18 with surgical delivery from 0.5 to 6h later. Differential gene expression was analyzed in the whole mouse brain using RT-PCR. When compared to control mice, pups exposed to LPS showed increased expression of pro-inflammatory genes monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), as well as VEGF, a regulator of vascular development and permeability, the anti-apoptotic protein Y-box-binding protein-1 (YB-1), and the neuronal differentiation factor necdin. LPS-exposed mice also showed downregulation of semaphorin 5b and groucho, involved in axon guidance and neurogenesis, respectively, providing evidence that LPS may disrupt normal developmental pathways. These data suggest possible mechanisms for adverse neurological outcomes following maternal infection involving elevated cytokine levels and altered expression of developmental genes in the fetal brain.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Mail Stop 3038, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
Christopher S
CS
Liverman
Harold A
HA
Kaftan
Lisa
L
Cui
Stephen G
SG
Hersperger
Eugenio
E
Taboada
Robert M
RM
Klein
Nancy E J
NE
Berman
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology; D016207:Cytokines / Q000145:classification / Q000378:metabolism*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D050437:Genes, Developmental / Q000187:drug effects*; D008070:Lipopolysaccharides; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger