Dynamic monitoring of depressive behavior induced by nonylphenol and its effect on synaptic plasticity in rats.
Dynamic monitoring of depressive behavior induced by nonylphenol and its effect on synaptic plasticity in rats.
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DOI：
10.1016/j.scitotenv.2019.06.250
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
Jie Yu;Weihong Xu;Ya Luo;W. Ou;Shengnan Li;Xu Chen;Jie Xu
中科院分区：
文献类型：
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作者：
Jie Yu;Weihong Xu;Ya Luo;W. Ou;Shengnan Li;Xu Chen;Jie Xu
抑郁症的病因尚不清楚，人们认为内分泌干扰物（EDCs）有助于疾病。我们前期的研究结果表明，壬基酚（nonylphenol，NP）具有神经毒性作用，但NP是否通过影响突触可塑性而诱发抑郁行为尚未明确。本文动态观察了亚慢性NP染毒诱导的大鼠抑郁行为及其对神经元突触可塑性的影响。将30只SD大鼠随机分为3组：对照组（C，玉米油）、NP组（NP，4 mg/kg）和抑郁模型组（D，皮质酮20 mg/kg）。每组8只大鼠。采用蔗糖偏好实验、旷场实验和强迫游泳实验检测大鼠抑郁行为，每月1次，连续3个月。采用酶联免疫吸附法（ELISA）检测血清中脑源性神经营养因子（BDNF）和皮质酮水平，苏木精-伊红（HE）染色观察细胞形态学变化。高尔基体染色观察神经细胞数、树突长度、树突棘密度;透射电镜观察突触间隙宽度、突触后密度（PSD）厚度、突触界面曲率。与对照组相比，NP组第2、3个月蔗糖液消耗量较第1个月减少（F = 9.887，P = 0.002）。中心方进入次数、中心方持续时间和总运动距离均减少，且3个月时减少程度大于1个月时（F = 21.191，P < 0.001; F = 9.836，P = 0.002）。术后1个月不动时间NP组明显高于对照组（F = 6.912，P = 0.002）。脑源性神经营养因子的表达高于对照组，而皮质酮的表达低于对照组。NP组神经细胞胞浆收缩，排列紊乱。NP组神经元排列紊乱，细胞数、树突顶端长度、基底树突长度及树突棘密度均低于对照组。与对照组相比，NP组PSD厚度、突触间隙宽度和突触界面曲率均减小。4 mg/kg NP亚慢性染毒可导致大鼠出现抑郁行为，且随着染毒时间的延长，抑郁行为和突触可塑性的改变更为明显。
The etiology of depression is not known, it is thought that endocrine-disrupting chemicals (EDCs) contribute to the disease. Results of our previous research have shown that nonylphenol (NP), a well-known EDC, has neurotoxic effects, however, whether NP can induce depressive behavior by affecting synaptic plasticity has not yet been clearly elucidated. The depressive behavior induced by subchronic exposure to NP and its effect on the neuronal synaptic plasticity in rats are dynamically observed. Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C, corn oil), NP group (NP, 4 mg/kg), and depression model group (D, corticosterone 20 mg/kg). There were 8 rats in each group. The depressive behavior of rats was tested by sucrose preference test, open-field test, and forced swimming test once a month for 3 months. The serum levels of brain-derived neurotrophic factor (BDNF) and corticosterone were detected by ELISA assay, and cellular morphological changes were observed by hematoxylin-eosin (HE) staining. The number of nerve cells, the length of dendrites, and the density of dendritic spines were observed by Golgi staining, and the synaptic cleft width, the postsynaptic density (PSD) thickness, and the synaptic interface curvature were observed by transmission electron microscope. Compared with the control group, the consumption of sucrose solution decreased in the NP group at the 2nd and 3rd month compared to the 1st month (F = 9.887, P = 0.002). The number of central square entries, the central square duration, and the total distance of movement were all decreased, and the decreasing degrees at the 3rd month were greater than those at the 1st month (F = 21.191, P < 0.001; F = 9.836, P = 0.002). The time of immobility for the NP group at the 1st month was higher than that in the control group (F = 6.912, P = 0.002). The expression of BDNF in the NP-treated group was higher than the control, while the expression of corticosterone in the NP-treated group was lower than the control. In the NP group, the cytoplasm of nerve cells contracted and appeared disordered. The neuron arrangement was disordered, and the number of cells, the length of the apex, the length of the basal dendrites, and the dendritic spine density were all lower in the NP group than those in the control group. The PSD thickness, the synaptic cleft width, and synaptic interface curvatures were all decreased in the NP group when compared to the control group. Subchronic exposure to 4 mg/kg NP led to depressive behavior in rats, and the depressive behavior and alterations in synaptic plasticity were more obvious with longer exposure time.