Selective cognitive impairments are related to selective hippocampus and prefrontal cortex deficits after prenatal chlorpyrifos exposure

Prenatal exposure to chlorpyrifos (CPF) leads to cognitive impairments in adulthood. The cytoarchitectural basis is unclear. In the present study, we assessed the effects of prenatal CPF exposure on T-maze delayed alternation task and the win-shift/lose-shift responses associated with the morphology of the dorsal hippocampus (dHPC) and the medial prefrontal cortex (mPFC) in adult animals. Gestational ICR female mice were exposed to 0, 1 or 5 mg/kg/d of CPF through gestational days 13-17. Behavioral experiments were performed on postnatal days (PD) 45-60 of the male and female offsprings; morphological samples were collected on PD 60. Our behavioral study results showed a gradual increase in the number of lose-shift errors on increased memory loads in the 5 mg/kg/d CPF-treated males. A weak initial increase in the number of lose-shift errors was observed in the females. In all of the groups, no significant differences were observed in the number of win-shift errors and correct of the first choice. The morphological studies showed extensive condensed nucleus and enlarged intercellular spaces in the CA1 and DG sub-regions in the dHPC of the CPF-treated males and the DG sub-region of the CPF-treated females. The cell count was significantly reduced in these sub-regions. The morphological studies showed no obvious abnormalities at PrL and IL of mPFC in the CPF-treated males and females, but the cell count was reduced. Our findings suggest that prenatal CPF exposure at 5 mg/kg/d induces selective cognitive impairments, which based on the morphological deficits in the dHPC and the mPFC. (C) 2012 Elsevier B.V. All rights reserved.