Intrauterine inflammation reduces postnatal neurogenesis in the hippocampal subgranular zone and leads to accumulation of hilar ectopic granule cells

Prenatal inflammation is associated with poor neurobehavioral outcomes in exposed offspring. A common route of exposure for the fetus is intrauterine infection, which is often associated with preterm birth. Hippocampal development may be particularly vulnerable to an inflammatory insult during pregnancy as this region remains highly neurogenic both prenatally and postnatally. These studies sought to determine if intrauterine inflammation specifically altered hippocampal neurogenesis and migration of newly produced granule neurons during the early postnatal period. Microglial and astroglial cell populations known to play a role in the regulation of postnatal neurogenesis were also examined. We show that intrauterine inflammation significantly reduced hippocampal neurogenesis between postnatal days 7 (P7) and P14 as well as decreased granule cell density at P28. Ectopic migration of granule cells was observed in LPS-exposed mice at P14, but not at P28. Intrauterine inflammation had no effect on hippocampal astrocyte or microglia density or on apoptosis rate at the postnatal time points examined. Thus, exposure to intrauterine inflammation disrupts early postnatal neurogenesis and leads to aberrant migration of newly born granule cells.