Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on spatial memory and NMDA receptor of hippocampus in mice
Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on spatial memory and NMDA receptor of hippocampus in mice
复制标题
子宫和哺乳期暴露于邻苯二甲酸二(2-乙基己基)酯对小鼠空间记忆和海马NMDA受体的影响
DOI：
10.1016/j.yhbeh.2015.03.008
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发表时间：
2015-05-01
影响因子：
3.5
通讯作者：
Hu, Yizhong
中科院分区：
文献类型：
--
作者：
Dai, Yuhua;Yang, Yanling;Hu, Yizhong
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种环境内分泌干扰物。目前，对DEHP在野生动物和人类中的神经发育毒性知之甚少。本研究调查了DEHP的影响，重点是从妊娠第7天到出生后第21天，在子宫和哺乳期暴露于DEHP（10、50和200 mg/kg/d）后，分别在6和12周龄的后代小鼠的行为变化。旷场任务的结果表明，DEHP增加了6周龄雄性和12周龄雌性的梳理，但降低了6周龄雌性的饲养频率和12周龄雌性的网格交叉次数。在Morris水迷宫任务中，50和200 mg/kg/d DEHP显著延长了6周龄雄性小鼠在水迷宫中搜索隐藏平台的时间，并减少了在目标象限中停留的时间，但6周龄雌性和12周龄雄性小鼠均未出现这种情况，表明围产期暴露于DEHP后，年轻雄性小鼠的空间学习和记忆受损。蛋白质印迹分析进一步表明，50和200 mg/kg/d的DEHP降低了6周龄雄性海马中N-甲基-D-天冬氨酸（NMDA）受体亚基NR 1和NR 2B的水平。这些结果表明，子宫和哺乳期暴露于低剂量的DEHP性别特异性影响的行为，包括运动活动和空间记忆，通过伴随抑制后代小鼠海马的NMDA受体。(C)2015 Elsevier Inc. All rights reserved.
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disrupter. Currently, little is known about neurodevelopmental toxicity of DEHP in wildlife and humans. The present study investigated the effects of DEHP, focusing on the changes in the behavior of offspring mice at the ages of 6 and 12 w, respectively, following utero and lactational exposure to DEHP (10, 50, and 200 mg/kg/d) from gestation day 7 through postnatal day 21. The results of open field tasks showed that DEHP increased the grooming of males at age 6w and females at age 12 w but decreased the frequency of rearing of 6-w-old females and the number of grid crossings of 12-w-old females. In the Morris water maze task, 50 and 200 mg/kg/d DEHP significantly prolonged the time of searching the hidden platform in water maze and reduced the time staying in the target quadrant during a probe trial of 6-w-old male mice, but not of 6-w-old females nor 12-w-old mice of both sexes, suggesting an impaired spatial learning and memory among younger males after perinatal exposure to DEHP. Western blot analyses further showed that DEHP at 50 and 200 mg/kg/d decreased the levels of the N-methyl-D-aspartic acid (NMDA) receptor subunits NR1 and NR2B in the hippocampus of 6-w-old males. These results suggest that uterine and lactational exposure to low doses of DEHP sex-specifically impacted behaviors, including locomotion activity and spatial memory, via the concomitant inhibition of the NMDA receptor of the hippocampus in offspring mice. (C) 2015 Elsevier Inc. All rights reserved.