Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice

Mol Psychiatry. 1999 Mar;4(2):145-54. doi: 10.1038/


Recent reports indicate an association between second trimester human influenza viral infection and later development of schizophrenia. Postmortem human brain studies also provide evidence for reduction in Reelin mRNA (an important secretory protein responsible for normal lamination of the brain) in schizophrenic brains. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of reelin in day 0 neonatal brains. Prenatally-infected murine brains from postnatal day 0 showed significant reductions in reelin-positive cell counts in layer I of neocortex and other cortical and hippocampal layers when compared to controls. Whereas layer I Cajal-Retzius cells produced significantly less Reelin in infected animals, the same cells showed normal production of calretinin and nNOS when compared to control brains. Moreover, prenatal viral infection caused decreases in neocortical and hippocampal thickness. These results implicate a potential role of prenatal viral infection in causation of neuronal migration abnormalities via reduction in Reelin production in neonatal brains.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Humans
  • Influenza A virus
  • Influenza, Human / complications*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Pregnancy
  • Pregnancy Complications, Infectious*
  • Prenatal Exposure Delayed Effects*
  • Reelin Protein
  • Reference Values
  • Schizophrenia / etiology
  • Schizophrenia / virology
  • Serine Endopeptidases


  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • RELN protein, human
  • Reln protein, mouse
  • Serine Endopeptidases