Chemistry and Life Sciences College, Zhejiang Normal University, China.
Chemistry and Life Sciences College, Zhejiang Normal University, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, China.
Horm Behav. 2014 Feb;65(2):106-13. doi: 10.1016/j.yhbeh.2013.12.004. Epub 2013 Dec 11.
Bisphenol-A (BPA), an environmental endocrine disruptor, has been reported to possess weak estrogenic, anti-estrogenic, and anti-androgen properties. Previous evidence indicates that perinatal exposure to low levels of BPA affects anxiety-like and cognitive behaviors in adult rodents. The present study aims to investigate the effect of BPA on emotional memory using the contextual fear conditioning of male mice in adulthood exposed to BPA for 90days. The results indicated that exposure to BPA increased the freezing time 1h and 24h after fear conditioning training. Furthermore, western blot analyses showed that BPA exposure decreased the level of N-methyl-d-aspartic acid (NMDA) receptor subunit NR1 and increased the expression of histone deacetylase 2 (HDAC2) before fear conditioning training in the hippocampus of male mice. One and twenty-four hours after fear conditioning training, BPA enhanced the changes of the expressions of NR1, phosphorylated extracellular regulated protein kinases (ERK1/2), and histone acetylation induced by contextual fear conditioning in the hippocampus. These results suggest that long term exposure to BPA enhanced fear memory by the concomitant increased level of NMDA receptor and/or the enhanced histone acetylation in the hippocampus, which may be associated with activation of ERK1/2 signaling pathway.
双酚 A(BPA)是一种环境内分泌干扰物,具有较弱的雌激素、抗雌激素和抗雄激素特性。先前的证据表明,围产期接触低水平的 BPA 会影响成年啮齿动物的焦虑样和认知行为。本研究旨在通过成年雄性小鼠的情景恐惧条件反射来研究 BPA 对情绪记忆的影响,这些雄性小鼠在 90 天内接触 BPA。结果表明,暴露于 BPA 会增加恐惧条件反射训练后 1 小时和 24 小时的冻结时间。此外,Western blot 分析显示,BPA 暴露会降低海马体中 N-甲基-D-天冬氨酸(NMDA)受体亚基 NR1 的水平,并在恐惧条件反射训练前增加组蛋白去乙酰化酶 2(HDAC2)的表达。在恐惧条件反射训练后 1 小时和 24 小时,BPA 增强了海马体中 NMDA 受体和/或组蛋白乙酰化水平的变化,这些变化是由情景恐惧条件反射引起的。这些结果表明,长期接触 BPA 通过同时增加 NMDA 受体水平和/或增强海马体中的组蛋白乙酰化来增强恐惧记忆,这可能与 ERK1/2 信号通路的激活有关。