Chemistry and Life Sciences College, Key Laboratory of Wildlife Biotechnology and Conservation and Utilization of Zhejiang Province, Zhejiang Normal University, PR China.
Chemistry and Life Sciences College, Key Laboratory of Wildlife Biotechnology and Conservation and Utilization of Zhejiang Province, Zhejiang Normal University, PR China; Zhejiang Provincial Key Laboratory of Ecology, Zhejiang Normal University, PR China.
Horm Behav. 2018 Jun;102:129-138. doi: 10.1016/j.yhbeh.2018.05.012. Epub 2018 May 25.
Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice. In forced swim task, BPA prolonged the total time of immobility of both sham and TP-GDX mice but not GDX mice. In addition, BPA reduced the levels of T in the serum and the brain of sham and TP-GDX mice. Western blot analysis further showed that BPA reduced the levels of androgen receptor (AR) and GABA(A)α2 receptor of the hippocampus and the amygdala in sham and inhibited the rescue of TP in these proteins levels of GDX mice. Meanwhile, BPA decreased the level of phospho-ERK1/2 in these two brain regions of sham and TP-GDX mice. These results suggest that long-term exposure to BPA inhibited TP-improved anxiety- and depression-like behaviors in GDX male mice. The down-regulated levels of GABA(A)α2 receptor and AR and an inhibited activity of ERK1/2 pathway in the hippocampus and the amygdala may be involved in these process.
双酚 A（BPA）是一种众所周知的环境内分泌干扰物。发育期暴露于 BPA 会影响多种模式生物的多种行为。我们最近的研究发现，成年期暴露于 BPA 会加重雄性小鼠的焦虑和抑郁样状态，但不会加重雌性小鼠的焦虑和抑郁样状态。在这项研究中，11 周龄去势（GDX）雄性小鼠每天接受丙酸睾酮（TP，0.5mg/kg）、TP 和 BPA（0.04、0.4 或 4mg/kg）或载体皮下注射，共 45 天。BPA（0.4 或 4mg/kg）不影响 GDX 小鼠高架十字迷宫任务，但缩短了假手术和 TP-GDX 小鼠的开放臂时间并减少了头浸次数。在强迫游泳任务中，BPA 延长了假手术和 TP-GDX 小鼠的不动时间，但不延长 GDX 小鼠的不动时间。此外，BPA 降低了假手术和 TP-GDX 小鼠血清和大脑中的 T 水平。Western blot 分析进一步表明，BPA 降低了假手术和 TP-GDX 小鼠海马和杏仁核中的雄激素受体（AR）和 GABA(A)α2 受体水平，并抑制了 GDX 小鼠中这些蛋白水平的 TP 恢复。同时，BPA 降低了这两个脑区中假手术和 TP-GDX 小鼠的磷酸化 ERK1/2 水平。这些结果表明，长期暴露于 BPA 抑制了 TP 改善 GDX 雄性小鼠的焦虑和抑郁样行为。海马和杏仁核中 GABA(A)α2 受体和 AR 水平下调以及 ERK1/2 通路活性受到抑制可能参与了这些过程。
