Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China; Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China; Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Environ Toxicol Pharmacol. 2013 Sep;36(2):392-402. doi: 10.1016/j.etap.2013.05.001. Epub 2013 May 9.
Dibutyl-phthalate (DBP) is a ubiquitous environmental contaminant. However, its neurotoxic effects on neonatal, immature or mature brains remain unclear. Here, we aimed to investigate the neurotoxicity of perinatal exposure of DBP on rodent offspring animals. Pregnant rats received intragastric DBP (500mg/kg body weight) daily from gestational day (GD) 6 to postnatal day (PND) 21. Animals in the control group received the same volume of edible corn oil. Brain sections or tissues from offspring rats on PND5, PND21 and PND60 were collected for analysis. Histological examination demonstrated that perinatal exposure of DBP resulted in hippocampal neuron loss and structural alternation in neonatal and immature offspring rats (PND5 and PND21), while no significant change was found in mature rats (PND60). DBP exposure induced cell apoptosis in hippocampal neurons of these neonatal and immature animals, as evidenced by the increased number of TUNEL-positive and Annexin V-propidium iodide (PI) positive cells and up-regulated caspase-3 activity. Moreover, DBP exposure decreased the expression of synaptophysin in the hippocampus and reduced both the slope and amplitude of field excitatory postsynaptic potentials (fEPSPs). DBP also impaired the spatial learning and memory of offspring rats. However, no significant difference in the susceptibility to DBP-induced neurotoxicity was found between male and female offspring rats. Our findings indicated that perinatal exposure of DBP could induce neurotoxicity in neonatal and immature offspring animals, but had no influence on mature animals after DBP withdrawal. These results may provide basic experimental evidence for better understanding the neurotoxic effects of DBP on neonatal, immature and mature brains.
邻苯二甲酸二丁酯（DBP）是一种普遍存在的环境污染物。然而，其对新生、未成熟或成熟大脑的神经毒性作用尚不清楚。在这里，我们旨在研究围产期 DBP 暴露对啮齿动物后代动物的神经毒性。妊娠大鼠从妊娠第 6 天（GD）至产后第 21 天（PND）每天接受胃内 DBP（500mg/kg 体重）。对照组动物接受相同体积的可食用玉米油。在 PND5、PND21 和 PND60 时收集后代大鼠的脑切片或组织进行分析。组织学检查表明，围产期 DBP 暴露导致新生和未成熟后代大鼠（PND5 和 PND21）海马神经元丢失和结构改变，而在成熟大鼠（PND60）中未发现明显变化。DBP 暴露诱导这些新生和未成熟动物海马神经元细胞凋亡，表现为 TUNEL 阳性和 Annexin V-碘化丙啶（PI）阳性细胞数量增加以及 caspase-3 活性上调。此外，DBP 暴露降低了海马体中突触小体蛋白的表达，并且减少了场兴奋性突触后电位（fEPSP）的斜率和幅度。DBP 还损害了后代大鼠的空间学习和记忆能力。然而，在 DBP 诱导的神经毒性易感性方面，雄性和雌性后代大鼠之间没有发现明显差异。我们的研究结果表明，围产期 DBP 暴露可引起新生和未成熟后代动物的神经毒性，但在 DBP 撤出后对成熟动物没有影响。这些结果可能为更好地理解 DBP 对新生、未成熟和成熟大脑的神经毒性作用提供基本的实验依据。
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