Reversible effect of developmental exposure to chlorpyrifos on late-stage neurogenesis in the hippocampal dentate gyrus in mouse offspring

Abstract

The effect of developmental exposure to chlorpyrifos (CPF) on hippocampal neurogenesis was examined in male mice after maternal dietary exposure to CPF at 0, 4, 20, or 100ppm from gestation day 10 to postnatal day (PND) 21. Cholinesterase activity was dose-dependently decreased in red blood cells at ≥4ppm and in the brain at 100ppm both in dams and offspring on PND 21. Immunohistochemically, doublecortin(+) cells were decreased at ≥20ppm in the subgranular zone (SGZ) of the dentate gyrus, and NeuN(+)-expressing mature neurons were decreased at 100ppm in the hilus on PND 21. There were no differences in the numbers of progenitor populations expressing Tbr2 or M1 muscarinic acetylcholine receptors. Transcript levels of Dcx also decreased at ≥20ppm, and those of Pcna, Casp3, Bax, Bcl2, Pax6 and Tbr2 were unchanged in the dentate gyrus by real-time RT-PCR. At PND 77, hippocampal neurogenesis was unchanged. These results suggest that developmental CPF exposure directly but transiently suppresses maturation of late-stage granule cell lineages in the SGZ and affects interneuron populations in the hilus.