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

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