Role of NMDA receptor in damage of learning and memory induced by sub-chronic aluminum exposure
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摘要: 目的探讨N-甲基-D-天门冬氨酸受体(NMDAR)在亚慢性染铝致大鼠学习记忆损害中作用。方法 健康成年雄性SD大鼠36只,按体重随机分为对照组、低、中、高剂量麦芽酚铝[Al(mal)3]组(0.41、0.81、1.23 mg/kg),腹腔注射染毒8周后,用Morris水迷宫试验检测大鼠空间学习记忆能力,苏木精-伊红(HE)染色观察大鼠海马组织病理变化,Western-blot方法检测大鼠海马组织NMDAR亚单位NR-2A、NR-2B表达。结果 中、高剂量组大鼠找到平台时间分别为(44.12±5.62)、(45.92±13.97)s,均长于对照组的(26.80±1.59)s(P<0.05);中、高剂量染铝组大鼠在目标象限停留时间均明显减少(P<0.05);随着铝剂量增加,大鼠海马锥体层细胞排列分散,细胞数目减少,出现核固缩、空泡变性等病理改变;与对照组NR-2A蛋白表达水平(0.69±0.03)比较,中、高剂量组表达水平均明显降低(P<0.05),且呈剂量效应关系;与对照组比较,各剂量染铝组大鼠NR-2B蛋白水平变化不明显。结论 亚慢性染铝可使大鼠学习记忆能力下降,其机制可能与大鼠海马NMDAR亚基蛋白表达改变有关。
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关键词:
- N-甲基-D-天门冬氨酸受体(NMDAR) /
- 铝 /
- 学习记忆 /
- 海马
Abstract: Objective To study the role of N-methyl-D-asparate (NMDA) receptor in the damage of learning and memory induced by sub-chronic aluminum exposure in rats.Methods Thirty-six healthy male adult Sprague-Dawley (SD) rats were randomly divided into normal saline,low,moderate,and high dose aluminium exposure group(0.41,0.81,and 1.23 mg/kg·w).The rats were exposed to Al(mal)3 with intraperitoneal injection for 8 weeks.After the exposure,Morris water maze test was performed to test the learning and memory abilities of the rats.Hematoxylin-eosin staining (HE) staining was employed to observe pathologic changes of hippocampus.The expression of NMDA receptor in moderate and hippocampus was detected with western blot.Results The time of platform-finding was prolonged for the rats in moderate and high dose exposure group (44.12±5.62 s,45.95±13.97 s) compared to that of rats in low dose exposure group(29.86±10.34s)(P<0.05).The dispersed arrangement,decreased cell nnmber,nuclei atrophy,and vacular degeration were observed in hipocapal pyramida cells of the rats with high dose aluminum exposure.Compare to that of the normal saline group,NMDAR receptor 2A protein of the rats in moderate(0.44±0.12) and high dose exposure group (0.32±0.19)was significantly decreased (P<0.05) in a dose-response manner.Compare to that of the control group,the expression of NMDA receptor-2B subunits protein was not significantly different in aluminum exposure groups.Conclusion Sub-chronic aluminum exposure could induce learning and memory damage in rats and its mechanisms may be associated with the chancg of NMDAR subunits protein expression.-
Keywords:
- NMDA receptor /
- aluminum /
- learning and memory /
- hippocampus
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