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[发育暴露于邻苯二甲酸二(2-乙基己基)酯对小鼠学习和记忆的影响]

[Effects of developmental exposure to DEHP on learning and memory of mice].

作者信息

Wu D J, Luo B B, Feng Q W, Wang Q N

机构信息

Department of Toxicology, Anhui Medical University, Hefei 230032, China.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017 Apr 20;35(4):241-245. doi: 10.3760/cma.j.issn.1001-9391.2017.04.001.

Abstract

To investigate the effects of developmental exposure to DEHP on learning and memory of mice. Male littermates of ICR mice randomly assigned to five experimental groups (=14 for each condition) on PND4 to receive distilled water, vehicle and 10, 50 and 200 mg/ (kg·d) DEHP from PND5 to PND38 by gavage, weighing and recording body weight of mice. Open field task were conducted on PND 26 and Morris water maze task were begun from PND30 to PND 37 to evaluate spontaneous exploration activity and emotion, spatial learning and memory performance of pubertal mice, respectively. On PND39, all animals were killed and hippocampi were isolated on ice, then total proteins of hippocampus were extracted, followed by determining the expression of PSD95 and synapsin I by western blotting. 200 mg/ (kg·d) DEHP significantly reduced the growth of body weight of mice and the time staying in the central area in open field, prolonged the time searching the hidden platform in Morris water maze (<0.05) . 50 mg/ (kg·d) DEHP didn't change the growth of body weight and the emotion (>0.05) , but reduced the percent of time and distance in the target quadrant during the probe trial of mice in Morris water maze (<0.05) . The results of western blotting showed that DEHP significantly reduced the expression of PSD95 in hippocampus of mice with all dose groups (<0.01) , but only 200 mg/ (kg·d) DEHP reduced the expression of synapsin I (<0.05) . Developmental exposure to DEHP can damage the development of synapse in hippocampus, adversely impacting spatial memory performance of mice at a dose that are insufficient to significantly influence the general development and result in anxiety.

摘要

为研究发育期暴露于邻苯二甲酸二(2-乙基己基)酯(DEHP)对小鼠学习记忆的影响。将ICR小鼠的雄性同窝幼崽在出生后第4天(PND4)随机分为五个实验组(每组每种情况14只),从出生后第5天(PND5)至出生后第38天(PND38)通过灌胃给予蒸馏水、溶媒以及10、50和200毫克/(千克·天)的DEHP,称量并记录小鼠体重。在出生后第26天进行旷场试验,从出生后第30天至出生后第37天开始进行莫里斯水迷宫试验,分别评估青春期小鼠的自发探索活动和情绪、空间学习和记忆能力。在出生后第39天,处死所有动物并在冰上分离海马体,然后提取海马体的总蛋白,随后通过蛋白质印迹法测定突触后致密蛋白95(PSD95)和突触素I的表达。200毫克/(千克·天)的DEHP显著降低了小鼠体重增长以及在旷场试验中在中央区域停留的时间,延长了在莫里斯水迷宫中寻找隐藏平台的时间(P<0.05)。50毫克/(千克·天)的DEHP对体重增长和情绪没有影响(P>0.05),但降低了小鼠在莫里斯水迷宫探索试验中在目标象限的时间百分比和距离百分比(P<0.05)。蛋白质印迹法结果显示,所有剂量组的DEHP均显著降低了小鼠海马体中PSD95的表达(P<0.01),但只有200毫克/(千克·天)的DEHP降低了突触素I的表达(P<0.05)。发育期暴露于DEHP会损害海马体中突触的发育,在剂量不足以显著影响整体发育并导致焦虑的情况下,对小鼠的空间记忆能力产生不利影响。

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