Institute of Ecology, Chemistry and Life Sciences College, Zhejiang Normal University, China.
Institute of Ecology, Chemistry and Life Sciences College, Zhejiang Normal University, China.
Chemosphere. 2015 Feb;120:258-66. doi: 10.1016/j.chemosphere.2014.07.021. Epub 2014 Aug 15.
Humans are routinely exposed to low levels of bisphenol A (BPA), an environmental endocrine disruptor, which is widely used in the production of polycarbonate plastics. The effects of perinatal exposure to BPA have been shown to affect various aspects of social behaviors such as anxiety and depression in adult offspring. Because sex hormones play a critical role in neurobehavior in adulthood, it is possible that long-term exposure to BPA has widespread effects on these emotional behaviors in adulthood. In the present study, adult mice were exposed to BPA at dosages of 0.04, 0.4, 4, 40 mg kg(-1)d(-1) for 12 weeks. A behavioral assay was performed using the open field test (OFT), mirrored maze, the elevated plus maze (EPM), and the forced swim task. The results showed that, after exposure to BPA at 0.4-40 mg kg(-1)d(-1), the number of open arm entries and the time spent in them in the elevated plus maze task were reduced in males but increased in females, and thus eliminating or reversing sex differences in these behaviors. BPA at 0.04-40 mg kg(-1)d(-1) increased the immobility of male mice in the forced swimming test. Furthermore, BPA (0.4-40 mg kg(-1)d(-1)) significantly decreased brain level of testosterone in males, but no significant influence was found in serum and the brain levels of estradiol in females. Western blot analysis further indicated that BPA at 0.4, 4, or 40 mg kg(-1)d(-1) significantly down-regulated the protein level of estrogen receptor β (ERβ) in the hippocampus of the adult males but not females, and inhibited the protein level of GABA(A)α2 receptor in hippocampus of males but promoted that of females. These results suggest that long-term exposure to BPA sex specifically affects anxiety- and depression-like behaviors in adult mice. Changes in the levels of GABA(A)α2 receptor and ERβ proteins of hippocampus might be associated with BPA-induced changes in these emotional behaviors.
人类经常接触到低水平的双酚 A（BPA），这是一种环境内分泌干扰物，广泛用于生产聚碳酸酯塑料。围产期接触 BPA 的影响已被证明会影响成年后代的各种社交行为，如焦虑和抑郁。由于性激素在成年期的神经行为中起着关键作用，因此长期暴露于 BPA 可能会对这些成年期的情绪行为产生广泛影响。在本研究中，成年小鼠以 0.04、0.4、4、40mgkg(-1)d(-1)的剂量暴露于 BPA 12 周。使用旷场试验（OFT）、镜像迷宫、高架十字迷宫（EPM）和强迫游泳试验进行行为测定。结果表明，在 0.4-40mgkg(-1)d(-1)BPA 暴露后，高架十字迷宫任务中进入开放臂的次数和在其中花费的时间减少，而在雌性中增加，从而消除或逆转了这些行为的性别差异。0.04-40mgkg(-1)d(-1)BPA 增加了雄性小鼠在强迫游泳试验中的不动性。此外，0.04-40mgkg(-1)d(-1)BPA 显著降低了雄性小鼠大脑中的睾酮水平，但在雌性中未发现血清和大脑中雌二醇水平的显著影响。Western blot 分析进一步表明，0.4、4 或 40mgkg(-1)d(-1)BPA 显著下调了成年雄性海马中的雌激素受体 β（ERβ）蛋白水平，但对雌性没有影响，并抑制了雄性海马中的 GABA(A)α2 受体蛋白水平，但促进了雌性海马中的蛋白水平。这些结果表明，长期暴露于 BPA 会特异性地影响成年小鼠的焦虑和抑郁样行为。海马中 GABA(A)α2 受体和 ERβ 蛋白水平的变化可能与 BPA 引起的这些情绪行为的变化有关。
