摘 要: 目的 研究纹状体内N-甲基-D天冬氨酸受体在锰致小鼠学习记忆功能障碍中的作用。方法 将48只昆明小鼠按体重随机分成4组,每组12只,雌雄各半,分别为对照组,12.5、25、50 mg/kg染锰组。腹腔注射,剂量为50 ml/kg,连续染毒2周,进行水迷宫以及避暗实验。处死小鼠,取纹状体,HE染色观察纹状体组织形态,电镜观察超微结构,免疫组化和Western blotting法测定NR2A和NR2B的表达。结果 水迷宫实验训练阶段的后期,50 mg/kg MnCl2组较同日对照组小鼠的逃避潜伏期和游泳距离增加;在6天和13天的检测阶段,50 mg/kg MnCl2组的小鼠穿环次数明显减少,25、50 mg/kg MnCl2组小鼠24 h后进入暗室的潜伏期明显缩短,次数明显增加。随着染锰剂量的增加,可见纹状体的组织形态发生病理性改变并出现超微结构损伤; 在25、50 mg/kg MnCl2组中,NR2A和NR2B的免疫组化表达的阳性面积比和积分光密度均明显下降,两者的蛋白水平亦明显降低,差异有统计学意义(P<0.05)。结论 锰通过干扰纹状体内NMDA受体的表达,造成小鼠学习记忆功能障碍。 |
关键词: 锰 NMDA受体 纹状体 学习 记忆 |
中图分类号: R994.3
文献标识码:
|
基金项目: |
|
Disturbance effect of manganese on learning and memory function in mice via interfering NMDA receptor of striatum |
Wang Can, Yang Xinxin, Song Qifan, Liu Wei, Xv Bin, Xv Zhaofa, Deng Yu
|
School of Public Health,China Medical University,Shenyang 110122,China
|
Abstract: Objective To investigate the effect of NMDAR of striatum on manganese-induced learning and memory dysfunction of mice. Methods Fourty-eight Kunming mice were randomly divided into control group and three MnCl2-exposed groups,twelve mice in each group,half male and half female. The control mice were treated with 0.9% NaCl, the Mn-exposed mice were treated with 12.5mg/kg,25mg/kg and 50 mg/kg MnCl2, respectively through intraperitoneal injection, once a day for two weeks. Then conduct the Morris water maze test and passive avoidance test, 24h after last passive avoidance test, all mice were sacrificed by decapitation after anesthesia and take the striatum. The morphological and ultrastrutural changes of striatum were observed by light and electron microscopes, meantime, the activities and protein levels of NR2A and NR2B were detected as well with immunohistochemical and Western blotting techniques. Results The results showed that at the later stage of Morris water maze test, the escape latent duration and swimming distance of mice in 50mg/kg MnCl2 group had some increase compared with that of control group, but at the 6th day and 13th day after administration, the frequency of crossing loop in mice of 50mg/kg MnCl2 group was obvious decreased as well as the latent duration of entering dark room after 24h of MnCl2 exposure, but the frequency of entering dark room was obviously increased. With the increase of Mn doses, there were some changes occurred both in the pathological structures and ultrastructures in striatums of mice, and the positive area and IOD (integral optical density) of the immunohistochemical expression of NR2A and NR2B as well the protein expression levels were all gone down. Conclusion The results showed that manganese may result in learning and memory dysfunction via disturbing the NMDAR of striatum. |
Keywords: manganese N-methyl-D-aspartate receptor (NMDAR) striatum learning memory |