Bisphenol-A antagonizes the rapidly modulating effect of DHT on spinogenesis and long-term potentiation of hippocampal neurons
Bisphenol-A antagonizes the rapidly modulating effect of DHT on spinogenesis and long-term potentiation of hippocampal neurons
复制标题
双酚 A 拮抗 DHT 对海马神经元棘生成和长期增强的快速调节作用
DOI：
10.1016/j.chemosphere.2017.12.086
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Xu Xiaohong
中科院分区：
文献类型：
--
作者：
Yang Yang;Fang Zhaoqing;Dai Yuhua;Wang Yu;Liang Yufeng;Zhong Xiaoyu;Wang Qinwen;Hu Yizhong;Zhang Zigui;Wu Donghong;Xu Xiaohong
双酚A(BPA)是一种常见的环境内分泌干扰物，在整个生命周期中调节雌激素、抗雌激素和抗雄激素的作用。最近的研究发现，BPA对男性某些神经行为的不良影响比女性更明显。在本研究中，10-100 NM的双酚A在1 小时内迅速增加培养的大鼠海马神经元树突棘和突触的密度，双酚A(100 NM)与双氢睾酮(DHT，10 NM)或17β-E_2(10 NM)共同处理可完全消除双氢睾酮或17β-E_2对树突棘和突触密度的促进作用。雌激素受体(ER)拮抗剂ICI182,780但不能阻断雄激素受体(ARs)拮抗剂氟他胺(Flu)30min可完全阻断BPA增强的树突棘和突触密度。在双酚A和双羟色胺之前预先给予氟他胺30min，可完全挽救双酚A增加的树突棘和突触的密度。此外，ERK1/2抑制剂U0126或p38抑制剂SB203580可完全消除BPA引起的树突棘和突触密度的增加。同时，双酚A(100 nM)可增强幼年雄性大鼠海马片齿状回的长时程增强效应，该作用不被氟他胺共同孵育所阻断，但可被P38抑制剂SB203580所抑制。BPA和DHT联合应用可抑制DHT抑制的LTP。这些结果首次证实了BPA对DHT在突触可塑性中的快速调节的拮抗作用。然而，BPA单独通过ER而不是AR来快速促进棘突发生和突触活动，ERKs和p38信号通路都参与了这些过程。
Bisphenol A (BPA), a common environmental endocrine disruptor, modulates estrogenic, antiestrogenic, and antiandrogenic effects throughout the lifespan. Recent studies found more obvious adverse effect of BPA on some neurobehavior in males than that in females. In this study, BPA at 10–100 nM rapidly increased the densities of the dendrite spine and synapse in cultured hippocampal neurons of ratsin vitrowithin 1 h. Co-treatment of BPA (100 nM) with dihydrotestosterone (DHT, 10 nM) or with 17β-E2(10 nM) completely eliminated the promotion of DHT or 17β-E2in the densities of the dendritic spine and synapse. Pretreatment of estrogen receptors (ERs) antagonist ICI182,780 but not of androgen receptors (ARs) antagonist flutamide (Flu) for 30min completely blocked BPA-enhanced densities of the dendritic spine and synapse. Pretreatment of flutamide for 30min before BPA and DHT completely rescued BPA-enhanced densities of the dendritic spine and synapse. Furthermore, pretreatment of ERK1/2 inhibitor U0126 or p38 inhibitor SB203580 entirely eliminated BPA-induced increases in the densities of the dendritic spine and synapse. Meanwhile, BPA (100 nM) enhanced long-term potentiation (LTP) induction of dentate gyrus in hippocampal slices of younger male rats, which was not blocked by co-incubation of flutamide but was inhibited by pretreatment of an P38 inhibitor SB203580. Co-application of BPA with DHT inhibited DHT-suppressed LTP. These results are the first demonstrating the antagonism of BPA to the rapid modification of DHT in synaptic plasticity. However, BPA alone rapidly promotes spinogenesis and synaptic activity through ER instead of AR, and both ERKs and p38 signaling pathways are involved in these processes.