Rapid proliferation of dentate gyrus progenitors in the ferret hippocampus following neonatal lipopolysaccharide exposure.

Lipopolysaccharide (LPS) plays a role in innate immunity and is used in animal models of maternal immune activation. The current study attempted to clarify the effect of LPS exposure on the dentate gyrus progenitors in ferret neonates.

Methods: LPS was administered subcutaneously at 500 μg/g of body weight to ferrets on postnatal days 6 and 7. Animals were injected intraperitonially with BrdU simultaneously with a second LPS injection to label the proliferating cells following LPS exposure.

Results: Two hours after BrdU injection, a significantly greater density of BrdU-labeled cells was observed in the hilus of the hippocampal dentate gyrus in LPS-exposed ferrets than in that of the controls. The majority of BrdU-labeled cells were Sox2 immunopositive in either the granular/subgranular layers or hilus in both groups. The percentages of BLBP (a marker of adult-type dentate gyrus progenitors), S100 (a marker of glial cells), and cleaved caspase 3 (a marker of apoptosis) were significantly lower in the granular/subgranular layers and/or hilus of LPS-exposed ferrets than in those of the controls.

Conclusions: These findings suggest that LPS promotes the proliferation of dentate gyrus progenitors. LPS may further act on the post-proliferative dentate gyrus progenitors to sustain their embryonic-type characteristics by preventing their transitions into the BLBP-expressing adult-type and/or S100-expressing glial cell lineages and by inhibiting programmed cell death.