Depressive behavior induced by nonylphenol and its effect on the expression of ER-α and ER-β in nerve cells of rats.
Depressive behavior induced by nonylphenol and its effect on the expression of ER-α and ER-β in nerve cells of rats.
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DOI：
10.1016/j.jad.2019.12.012
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发表时间：
2019-12
影响因子：
6.6
通讯作者：
Weihong Xu;Jie Yu;Shengnan Li;Jie Xu
中科院分区：
文献类型：
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作者：
Weihong Xu;Jie Yu;Shengnan Li;Jie Xu
目的：探讨壬基酚（NP）暴露对大鼠抑郁行为的影响，以及对神经细胞内雌激素受体-α (ER-α)和雌激素受体-β (ER-β)表达的影响。方法：选取雄性SD大鼠40只，随机分为空白对照组（0 mg/kg）、低剂量组（0.4 mg/kg）、中剂量组（4 mg/kg）、高剂量组（40 mg/kg） 4组，连续暴露NP 180 d。HT22 NP暴露剂量为20μM，分为空白对照组、NP组、ICI182780组和ICI182780+NP组。结果：在体内，在空地实验中，与对照组相比，NP高剂量组中央区进入次数和中央区注意时间逐渐减少（F= 3.561,p= 0.029）。在强迫游泳实验中，随着NP剂量的增加，静止时间增加，且中剂量组和高剂量组的增加程度均高于低剂量组（F= 3.047,p= 0.048）。中、高剂量组血清多巴胺（DA）浓度较对照组显著降低（F= 3.967,p= 0.023）。与对照组相比，4 mg/kg和40 mg/kg剂量的NP暴露诱导血清皮质酮水平升高（F= 11.536,p< 0.001）。与对照组相比，各NP处理组ER-β表达随NP剂量的增加而逐渐降低（F= 4.513,p= 0.014）。在体外，HT22细胞活性随NP剂量的增加而降低（F= 316.6,p< 0.001）。当NP剂量为200 μM时，HT22细胞的生长抑制率为（0.54±0.11）%。ICI182780+NP组ER-α和ER-β表达水平低于对照组和ICI182780组，高于NP组（F= 1.592,p= 0.266；F= 10.166,p= 0.004）。结论：长期暴露NP可引起大鼠抑郁行为、海马神经递质水平及内质网表达的改变。NP可降低HT22细胞的体外活性，降低ER-α和ER-β的表达水平。
Objective: To investigate the effects of nonylphenol (NP) exposure on the depressive behavior in rats, and the effects of the expressions of estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β) in nerve cells in vivo and vitro.Methods: Forty male SD rats were randomly divided into 4 groups: blank control group (0 mg/kg), low dose group (0.4 mg/kg), middle dose group (4 mg/kg) and high dose group (40 mg/kg), which were exposed to NP for 180 days. The exposure dose of NP in HT22 was 20μM, which was divided into4 groups: blank control group, NP group, ICI182780 group and ICI182780+NP group.Results: In vivo, in the open field experiment, the number of entries in the central area and duration of attention in central square decreased gradually in the NP high dose group compared with the control (F= 3.561,p= .029). In forced swimming experiment, with the increase of NP dose, the immobility time increased, and the increasing degree of middle dose group and high dose group was higher than that of the low dose group (F= 3.047,p= .048). The concentrations of serum dopamine (DA) in the middle dose and high dose groups decreased greatly compared with the control (F= 3.967,p= .023). NP exposure at the doses of 4 mg/kg and 40 mg/kg induced an increase in the level of serum corticosterone compared to the control (F= 11.536,p<.001). Compared with the control group, the expression of ER-β decreased gradually with an increase of NP dose in the NP treatment groups (F= 4.513,p= .014). In vitro, the activity of HT22 cells decreased with an increase of NP dose (F= 316.6,p<.001). When the dose of NP was 200 μM, the growth inhibition rate of HT22 cells was (0.54±0.11)%. The expression levels of ER-α and ER-β in ICI182780+NP group was lower than those in the control and ICI182780 groups, but higher than those in the NP group (F= 1.592,p=.266;F= 10.166,p=.004).Conclusion: Long-term exposure to NP could induce the alterations in depressive behavior, and the levels of neurotransmitters as well as the expression of ER in the hippocampus of rats. Moreover, NP could reduce the activity of HT22 cells and decrease the expression levels of ER-α and ER-β in vitro.