The toxic influence of paraquat on hippocampus of mice: Involvement of oxidative stress
The toxic influence of paraquat on hippocampus of mice: Involvement of oxidative stress
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DOI：
10.1016/j.neuro.2010.02.006
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发表时间：
2010-06-01
期刊：
影响因子：
3.4
通讯作者：
Liu, Rujun
中科院分区：
文献类型：
--
作者：
Chen, Qing;Niu, Yujie;Liu, Rujun
环境暴露于百草枯（PQ）已被认为是神经退行性疾病如帕金森病（PD）的潜在危险因素。海马体在大脑的学习和记忆能力中起着重要作用。本研究旨在探讨百草枯对小鼠海马的毒性作用及其机制。昆明小鼠随机分为4组（1个对照组和3个治疗组），剂量分别为0、0.89、2.67和8 mg/kg体重。百草枯口服，每天1次，连续28天。经百草枯处理后，海马细胞呈不规则状，胞浆浓缩。小体减少，神经元凋亡或坏死。Morris水迷宫实验表明，施用百草枯后，反应潜伏期明显增加。小鼠海马中丙二醛（MDA）水平和活性氧（ROS）的生成明显增加。百草枯处理后小鼠海马总超氧化物歧化酶（SOD）活性明显降低。对海马能量代谢的分析显示，百草枯处理后海马中三磷酸腺苷（ATP）浓度明显下降，这表明海马神经细胞线粒体的能量合成下降。百草枯处理后线粒体DNA （mtDNA）中8-OHdG水平显著升高，表明mtDNA氧化损伤加重。提示百草枯对小鼠海马具有毒性影响，其毒性机制可能与氧化应激诱导海马神经细胞线粒体损伤有关。(C) 2010爱思唯尔公司版权所有。
Environmental paraquat (PQ) exposure has been suggested to be a potential risk factor for neurodegenerative disorders such as Parkinson's disease (PD). The hippocampus plays an important role in the learning and memory abilities of the brain. This study aims to demonstrate the effect and mechanism of paraquat toxicity on the hippocampus of mice. Kunming mice were randomly divided into four groups (one control and three treatment groups) and the dosage levels were defined as 0, 0.89, 2.67 and 8 mg/kg body weight. Paraquat was given orally, once a day and for 28 consecutive days. After treatment with paraquat, the hippocampus cells were found to be irregular and the cytoplasm was found to be condensed. The nissl bodies were reduced and apoptotic or necrotic neuron was observed. Morris water maze tests showed that the response latency increased significantly in animals that were administered paraquat. The level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus of mice increased significantly. The activities of total superoxide dismutase (SOD) in the hippocampus of mice decreased significantly after treatment with paraquat. An analysis of the energy metabolism of hippocampus showed that the concentration of adenosine-triphosphate (ATP) decreased significantly in the hippocampus after treatment with paraquat, which implied that the energy synthesis of mitochondria with hippocampal neurocytes declined. The level of 8-OHdG in mitochondrial DNA (mtDNA) increased significantly after treatment with paraquat, which indicated that the oxidative damage of mtDNA increased. This suggests that paraquat had a toxic influence on the hippocampus of mice, and that the mechanism of toxicity might be associated with the mitochondrial injury of hippocampal neurocytes induced by oxidative stress. (C) 2010 Elsevier Inc. All rights reserved.