Clarification of the effects of diethylstilbestrol, an endocrine disruptors, on synaptic plasticity and its application as an detailed test

阐明内分泌干扰物己烯雌酚对突触可塑性的影响及其作为详细测试的应用

• 批准号: 15590110
• 负责人: SHIRASAKI Tetsuya
• 金额: $ 2.3万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590110/
• 关键词: endocrine disrupters; diethylstilbestrol; estrogen receptors; synaptic plasticity; LTP; LTD; hippocampus; proteome analysis; 内分泌撹乱物質; DES; 長期増強

Diethylstilbestrol(DES) 100 ng dissolved in 30 μl corn oil or corn oil alone was administered orally to ddY mice once a day from gestation day 11 to 17. When performed at post natal week(PNW) 6, long term potentiation(LTP) in the hippocampal CA1 was enhanced in DES exposure group. On the other hand, long term depression(LTD) was abolished at PNW6 in DES exposure group. Enhancement of LTP was related to the learning disability in the passive avoidance test. Preliminary data in estrogen receptor knock out mice showed the possibility that ERα might contribute to the DES-induced effects on the synaptic plasticity. To elucidate this possibility, further studies are necessary in the future. Proteome analysis revealed that the levels of at least 9 proteins were changed by more than 2 times in prenatal DES exposure group. Three of them were possibly lactate dehydrogenase, lactate dehydrogenase 2 and tubulin alpha. Nothing, however, is known about whether or not these substances are involved in the synaptic plasticity. No effect of prenatal DES exposure in female mice was observed. Further studies are needed to clarify the sexual differences in the effect of DES on the synaptic plasticity.The effect of prenatal exposure of DES on the LTP depended on condition of frequency stimulation, that is, stimulation with 50 Hz 30 pulses was more effective to induce LTP than that with 20 Hz 100 pulses. Effects of prenatal DES exposure on LTP and LTD were the most prominent at PNW6. In vitro experiment suggested that the effect of DES on LTP, which may be mediated through estrogen receptors, was weaker than 17β-estradiol. In conclusion, combination of two experimental protocols, effect on the LTP caused by 50 Hz 30 pulses and effect on the LTD caused by 1 Hz 900 pulses, might be useful for verifying effect on the synaptic plasticity of environmental disrupters possessing estrogenic activity such as DES.

从妊娠第 11 天到第 17 天，将 100 ng 己烯雌酚 (DES) 溶解在 30 μl 玉米油中或单独给 ddY 小鼠口服，每天一次。 DES暴露组的海马CA1增强，另一方面，DES暴露组的PNW6消除了长期抑郁（LTD）。在雌激素受体敲除小鼠中，LTP 的增强与学习障碍有关。为了阐明这种可能性，需要进一步研究。蛋白质组分析显示，产前DES暴露组中至少有9种蛋白质的水平发生了2倍以上的变化，其中3种可能是乳酸脱氢酶、乳酸。然而，对于这些物质是否参与突触可塑性尚不清楚，未观察到产前 DES 暴露对雌性小鼠的影响。 DES对突触可塑性的影响。产前暴露于DES对LTP的影响取决于频率刺激的条件，即50 Hz 30脉冲刺激比50 Hz 30脉冲刺激更能有效诱导LTP。 20 Hz 100 脉冲。产前 DES 暴露对 LTP 和 LTD 的影响在 PNW6 时最为显着。 体外实验表明 DES 对 LTP 的影响可能通过雌激素受体介导，但比 17β-雌二醇弱。 ，两个实验方案的组合，50 Hz 30 个脉冲对 LTP 的影响和 1 Hz 900 个脉冲对 LTD 的影响，可能有助于验证具有雌激素活性的环境干扰物（例如 DES）对突触可塑性的影响。