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

已烯雌酚(DES)10 0 ng溶于30μL玉米油或玉米油，d1 1~1 7d灌胃给药。生后第6周给予DES组小鼠海马区长时程增强。另一方面，DES暴露组在PNW6取消了长期抑郁(LTD)。LTP的增强与被动回避实验中的学习障碍有关。雌激素受体基因敲除小鼠的初步数据表明，ERα可能参与了DES对突触可塑性的影响。为了阐明这种可能性，未来有必要进行进一步的研究。蛋白质组分析显示，产前DES暴露组至少有9种蛋白质的水平发生了2倍以上的变化。其中3个可能是乳酸脱氢酶、乳酸脱氢酶2和微管蛋白α。然而，关于这些物质是否参与突触可塑性尚不清楚。未观察到孕期接触DES对雌性小鼠的影响。DES对突触可塑性影响的性别差异有待进一步研究。产前DES对LTP的影响依赖于频率刺激条件，即50 Hz30脉冲刺激比20 Hz100脉冲刺激更有效。产前DES暴露对LTP和LTD的影响在PNW6时最为显著。体外实验表明，DES对LTP的作用弱于17β-雌二醇，其作用可能是通过雌激素受体介导的。综上所述，50 Hz30脉冲对LTP的影响和1 Hz900脉冲对LTP的影响两种实验方案相结合，可能有助于验证DES等具有雌激素活性的环境干扰物对突触可塑性的影响。

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.