College of Biological and Environmental Engineering, Zhejiang University of Technology, 18 Chao-Wang Road, Hangzhou 310014, China.
Brain Res. 2012 Sep 20;1474:19-28. doi: 10.1016/j.brainres.2012.07.036. Epub 2012 Jul 25.
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 5mg/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 5mg/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 5mg/kg/d induces selective cognitive impairments, which based on the morphological deficits in the dHPC and the mPFC.
孕期接触毒死蜱（CPF）会导致成年后认知障碍。但其细胞结构基础尚不清楚。在本研究中，我们评估了孕期 CPF 暴露对 T 迷宫延迟交替任务的影响，以及与背侧海马（dHPC）和内侧前额叶皮层（mPFC）形态相关的赢-移/输-移反应，在成年动物中。妊娠 ICR 雌性小鼠在妊娠第 13-17 天经口给予 0、1 或 5mg/kg/d 的 CPF。雄性和雌性后代在出生后第 45-60 天进行行为实验；在 PD60 收集形态学样本。我们的行为研究结果表明，在记忆负荷增加的情况下，5mg/kg/d CPF 处理的雄性幼鼠的输-移错误次数逐渐增加。在雌性幼鼠中观察到初始数量的输-移错误略有增加。在所有组中，赢-移错误和第一选择的正确数量均无显著差异。形态学研究显示，CPF 处理雄性幼鼠的 dHPC 的 CA1 和 DG 亚区以及 CPF 处理雌性幼鼠的 DG 亚区的细胞核明显浓缩，细胞间隙增大。这些亚区的细胞计数明显减少。形态学研究显示 CPF 处理的雄性和雌性幼鼠的 mPFC 的 PrL 和 IL 无明显异常，但细胞计数减少。我们的研究结果表明，5mg/kg/d 的孕期 CPF 暴露会导致选择性认知障碍，这是基于 dHPC 和 mPFC 的形态缺陷。
