Effect of di-n-butyl phthalate on the cognitive function in offspring rats after perinatal exposure and its mechanism

Abstract:

Objective：To study the neurotoxicity of di-n-butyl phthalate（DBP） exposure on offspring rats and explore the underlying mechanism. Methods：Pregnant SD rats were randomly divided into three groups；50 mg/（kg·d） DBP（low-dose treatment group，n=10），200 mg/（kg·d） DBP（high-dose treatment group，n=10） or vehicle only（control group，n=8） was given respectively by gavage once a day from gestation day-6（GD6） to postnatal day-23（PND23） consecutively. The general effects of DBP on pregnant and off－spring rats were observed. The cognitive function of the offspring was evaluated through Morris water maze. The brain activity was recorded with electrocorticography. The morphological changes of the hippocampus were observed via HE staining. The expression levels of brain-derived neurotrophic factor（BDNF），neuropeptide Y（NPY） and estrogen receptor β（ERβ） protein in the hippocampus were measured by Western blot analysis. Results：Compared with those of the same sex in the control group，the pups in the high-dose treatment group showed lower birth weight（P<0.05）. In the water maze test，the escaping latency of both treatment groups was longer than that of the control（P<0.05）. The pups in the treatment groups also spent less time in the target quadrant（P<0.05），and the num－bers of crossing the platform were fewer，too（P<0.05）. During EEG recording，the pups in DBP treatment groups were found to have more delta activity（P<0.05） and delta+theta activity（P<0.01），but less theta and alpha activity（P<0.05）. HE staining showed that in the high-dose treatment group，the cell number in CA3 and DG region of the hippocampus decreased slightly，and so did the cell density. Furthermore，the expressions of BDNF，NPY and ERβ protein in the hippocampus were significantly reduced in both treatment groups（P<0.01）. Conclusion：DBP could cause cognitive dysfunction and slower brain rhythms in offspring rats after perinatal exposure，which may be related to the down-regulated expressions of BDNF，NPY and ERβ.