Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection

• Published in: Neuroscience letters 2006-05, Vol.399 (3), p.220-225
• Main Authors: Liverman, Christopher S., Kaftan, Harold A., Cui, Lisa, Hersperger, Stephen G., Taboada, Eugenio, Klein, Robert M., Berman, Nancy E.J.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Brain - drug effects; Brain - embryology; Cerebral palsy; Cytokines - classification; Cytokines - metabolism; Disease Models, Animal; Embryo, Mammalian; Female; Gene Expression - drug effects; Genes, Developmental - drug effects; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Lipopolysaccharide; Lipopolysaccharides; Maternal infection; Medical sciences; Mice; Nervous system (semeiology, syndromes); Neurology; Periventricular leukomalacia; Pregnancy; Prenatal Exposure Delayed Effects; Pro-inflammatory cytokines; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Time Factors
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.01.064

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 μg LPS or saline on E18 with surgical delivery from 0.5 to 6 h 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-1β (IL-1β), 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.