Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Synapse. 2010 Jun;64(6):432-9. doi: 10.1002/syn.20746.
Bisphenol A (BPA), an environmental endocrine-disrupting chemical, has been extensively evaluated for reproductive toxicity and carcinogenicity. However, little is known about the behavioral and neurochemical effects of BPA exposure. This study examined whether chronic daily exposure to an environmental endocrine-disrupting chemical, bisphenol A [(BPA); 100 microg/kg/day or 500 microg/kg/day, p.o.], from prenatal Day 7 to postnatal Day 36 would lead to changes in anxiety and memory in mice. First, we observed the behavioral alterations of BPA-treated mice using two anxiety-related models, the open field test and elevated plus maze (EPM) test. In the open field test, BPA treatment (100 microg/kg/day) increased movement in the central zone. BPA treatment (500 microg/kg/day) also increased the time spent in the open arms in the EPM test. Second, we measured cognitive ability in the Y-maze test and novel object test. BPA-treated mice showed decreased alternation behavior in the Y-maze at both of doses, indicating working memory impairment. BPA-treated mice (100 microg/kg/day) also showed decreased novel object recognition as expressed by central locomotion and frequency in the central zone, showing recognition memory impairment. Finally, to measure changes in the dopaminergic and NMDAergic systems in the brain, we performed autoradiographic receptor binding assays for dopamine D(1) and D(2) receptors, the NMDA receptor, and the dopamine transporter. BPA treatment increased D(2) receptor binding in the caudate putamen (CPu) but decreased DAT binding. BPA treatment also decreased NMDA receptor binding in the frontal cortex and CA1, CA3, and DG of the hippocampus. Taken together, our results suggest that long-term BPA exposure in mice can induce anxiolytic behaviors, cognitive deficits and changes in the dopaminergic and NMDAergic systems.
双酚 A（BPA）是一种环境内分泌干扰化学物质，其生殖毒性和致癌性已得到广泛评估。然而，人们对 BPA 暴露的行为和神经化学影响知之甚少。本研究探讨了从产前第 7 天到产后第 36 天，慢性每日暴露于环境内分泌干扰化学物质双酚 A（BPA）[（BPA）；100μg/kg/天或 500μg/kg/天，口服]是否会导致小鼠焦虑和记忆发生变化。首先，我们使用两种焦虑相关模型（旷场试验和高架十字迷宫试验）观察了 BPA 处理小鼠的行为改变。在旷场试验中，BPA 处理（100μg/kg/天）增加了中央区域的运动。BPA 处理（500μg/kg/天）也增加了 EPM 测试中开放臂的时间。其次，我们在 Y 迷宫测试和新物体测试中测量了认知能力。两种剂量的 BPA 处理均导致 Y 迷宫中的交替行为减少，表明工作记忆受损。BPA 处理（100μg/kg/天）的小鼠还表现出中央运动和中央区域频率降低，表明识别记忆受损。最后，为了测量大脑中多巴胺能和 NMDA 能系统的变化，我们进行了多巴胺 D1 和 D2 受体、NMDA 受体和多巴胺转运蛋白的放射性配体结合测定。BPA 处理增加了尾壳核（CPu）中的 D2 受体结合，但降低了 DAT 结合。BPA 处理还降低了前额皮质和海马 CA1、CA3 和 DG 中的 NMDA 受体结合。总之，我们的结果表明，长期 BPA 暴露可导致小鼠产生焦虑样行为、认知缺陷以及多巴胺能和 NMDA 能系统的改变。
