Chemistry and Life Sciences College, Zhejiang Normal University, PR China.
Horm Behav. 2012 Sep;62(4):480-90. doi: 10.1016/j.yhbeh.2012.08.005.
Bisphenol-A (BPA), an environmental endocrine disruptor, has attracted attention because of its adverse effects on the brain and behavioral development. 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 changes of anxiety- and depression-like behaviors of perinatally exposed mice in adulthood following the gestational (gestation days 7 to 20) or lactational (postnatal days 1 to 14) exposure to BPA (0.4 or 4 mg/kg/d). The results indicated that both gestational and lactational exposures to BPA increased anxiety and depression-like behavior in mice of both sexes. The females with gestational exposure exhibited an increased anxiety-like state in the four models tested, including the open field, dark-light transition task, mirrored maze, and elevated plus maze tasks. Furthermore, the females with lactational exposure and the males with gestational exposure exhibited an anxiogenic-like behavior in two models, whereas the males with lactational exposure exhibited an anxiogenic-like behavior only in the elevated plus maze test. The results of the forced swim task showed that gestational exposure markedly increased the immobile time in both sexes, and the same effect was induced by lactational exposure only with 4 mg/kg/d BPA. Furthermore, western blot analyses showed that both gestational and lactational exposures inhibited the expression of the AMPA receptor subunit GluR1 in the hippocampus and amygdala in mice of both sexes, whereas the level of the NMDA receptor subunit NR1 was increased in the amygdala following gestational exposure but was reduced in the hippocampus of the females with lactational exposure. These results suggest that both gestational and lactational exposures to BPA increased anxiety- and depression-like behaviors of adult mice of both sexes. In addition gestational exposure exhibited a stronger effect on anxiety-like state in females. The altered levels of AMPA and NMDA receptors in the hippocampus and amygdala may be associated with BPA-induced behavioral changes.
双酚 A（BPA）作为一种环境内分泌干扰物，因其对大脑和行为发育的不良影响而受到关注。先前的证据表明，围产期低水平暴露于 BPA 会影响成年啮齿动物的焦虑样和认知行为。本研究旨在探讨围产期暴露于 BPA（0.4 或 4mg/kg/d）对成年小鼠焦虑和抑郁样行为的影响，BPA 的暴露途径分别为妊娠期（妊娠第 7 天至第 20 天）或哺乳期（产后第 1 天至第 14 天）。结果表明，妊娠期和哺乳期暴露于 BPA 均可增加雌雄小鼠的焦虑和抑郁样行为。妊娠期暴露的雌性小鼠在四种测试模型中均表现出焦虑样状态增加，包括旷场、明暗过渡任务、镜像迷宫和高架十字迷宫任务。此外，哺乳期暴露的雌性小鼠和妊娠期暴露的雄性小鼠在两种模型中表现出焦虑样行为，而哺乳期暴露的雄性小鼠仅在高架十字迷宫测试中表现出焦虑样行为。强迫游泳试验的结果表明，妊娠期暴露显著增加了雌雄小鼠的不动时间，而哺乳期暴露仅在 4mg/kg/d BPA 时也产生了相同的效果。此外，Western blot 分析表明，妊娠期和哺乳期暴露均抑制了雌雄小鼠海马和杏仁核中 AMPA 受体亚基 GluR1 的表达，而妊娠期暴露增加了杏仁核中 NMDA 受体亚基 NR1 的水平，但减少了哺乳期暴露的雌性小鼠海马中的 NR1 水平。这些结果表明，妊娠期和哺乳期暴露于 BPA 均可增加成年雌雄小鼠的焦虑和抑郁样行为。此外，妊娠期暴露对雌性小鼠的焦虑样状态影响更强。海马和杏仁核中 AMPA 和 NMDA 受体水平的改变可能与 BPA 诱导的行为变化有关。
