Prenatal viral infection of mice at E16 causes changes in gene expression in hippocampi of the offspring

Eur Neuropsychopharmacol. 2009 Sep;19(9):648-53. doi: 10.1016/j.euroneuro.2009.03.004. Epub 2009 Jun 5.

Abstract

The hippocampus governs memory formation and emotional regulation, and there is widespread evidence of hippocampal dysfunction in psychiatric disorders, including schizophrenia and autism. There is abundant evidence that prenatal viral infection may play a role in the development of these two disorders. In the current study, we have examined gene expression and structural changes of the hippocampi of exposed neonates following maternal infection at embryonic day (E) 16 (middle second trimester). We observed significant changes in gene expression in the offspring at postnatal day (P) 0 (birth), P14 (childhood), and P56 (adulthood), including a number of candidate genes for autism and schizophrenia. qRT-PCR verified the direction and magnitude of change for 5 of the genes from the microarray data set and revealed mRNA changes for additional genes associated with schizophrenia and autism. MRI revealed a decrease in hippocampal volume at P35 (adolescence). Our results demonstrate altered gene expression and reduced hippocampal volume in the offspring following prenatal viral infection at E16.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn / genetics*
  • Animals, Newborn / virology*
  • Autistic Disorder / genetics
  • Autistic Disorder / virology
  • Female
  • Fetal Diseases / genetics*
  • Fetal Diseases / virology*
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Hippocampus / pathology
  • Hippocampus / virology*
  • Infectious Disease Transmission, Vertical*
  • Influenza A Virus, H1N1 Subtype
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / genetics*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / transmission*
  • Pregnancy
  • Schizophrenia / genetics
  • Schizophrenia / virology