解剖学报

解剖学报 ›› 2014, Vol. 45 ›› Issue (1): 15-19.doi: 10.3969/j.issn.0529-1356.2014.01.003

• 神经生物学 • 上一篇    下一篇

快速老化小鼠P8海马神经元突触可塑性相关的AMPA受体表达异常

封敏1,2 ,张英俊3 ,鲁娟2 ,熊殷艺2 ,吴巧凤2 ,于美玲4, 卢圣锋5 ,余曙光2*   

  1. 1.怀化医学高等专科学校针灸推拿教研室，湖南 怀化 418000; 2.成都中医药大学时间生物学实验室，成都 610075;3. 怀化医学高等专科学校医学影像学教研室，湖南 怀化 418000; 4.南京中医药大学康复治疗学教研室，南京 210023;5.南京中医药大学针药结合省部共建教育部重点实验室，南京 210023
  • 收稿日期:2013-01-25 修回日期:2013-04-30 出版日期:2014-02-06 发布日期:2014-02-06
  • 通讯作者: 封敏 E-mail:fengminfengmin@sina.com
  • 基金资助:

    湖南省教育厅资助项目；怀化医学高等专科学校资助项目;国家自然科学基金资助项目;自然科学基金资助项目

Abnormal expression of AMPA receptor in hippocampus of senescence accelerated mouse prone 8 correlated to synaptic plasticity

FENG Min 1,2  ZHANG Ying-jun3  LU Juan2  XIONG Yin-yi2  WU Qiao-feng2  YU Mei-ling4  LU Sheng-feng5  YU Shu-guang 2*   

  1. 1.Department of Acupuncture and Moxibustion, Huaihua Medical College, Hu’nan Huaihua 418000,China;2. Laboratory of Chronobiology，Chengdu University of Traditional Chinese Medicine，Chengdu 610075，China;3.Department of Medical Imageology, Huaihua Medical College, Hu’nan Huaihua 418000,China;4.Department of Rehabilitation Therapy,Nanjing University of Chinese Medicine, Nanjing 210023，China;5.Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese 
    Medicine, Nanjing 210023，China）
  • Received:2013-01-25 Revised:2013-04-30 Online:2014-02-06 Published:2014-02-06

摘要：

目的 比较快速老化小鼠P8（SAMP8）与抗快速老化小鼠R1（SAMR1）海马神经元突触可塑性相关的谷氨酸α-氨基-3-羟基-5-甲基-4-异唑丙酸（AMPA）受体表达差异，为阿尔兹海默病（AD）的发病机制提供实验依据。 方法 取雄性10月龄SAMP8 10只和SAMR1 9只，应用Morris水迷宫实验评价动物学习记忆能力，透射电子显微镜观察海马CA1区神经元突触界面超微结构，蛋白质免疫印迹法检测海马AMPA受体亚基GluR1、GluR2的表达。 结果 与SAMR1比较，SAMP8逃避潜伏期延长，目标象限时间百分比下降，穿台次数减少；海马CA1区神经元突触后致密带变薄，突触间隙增宽，突触界面曲率下降；海马GluR2含量下降，GluR1含量有下降趋势，但差异无统计学意义。 结论 海马AMPA受体异常可能是导致突触可塑性受损，引发SAMP8认知障碍的原因之一，AMPA受体在AD的发病中可能占有重要地位。

关键词: 快速老化小鼠P8, 阿尔兹海默病, 谷氨酸α-氨基-3-羟基-5-甲基-4-异唑丙酸受体, 突触可塑性, 学习记忆, Morris水迷宫, 免疫印迹法, 小鼠

Abstract:

Objective To observe the expression differences of AMPA receptor in hippocampal neurons between SAMP8 and SAMR1 and to explore the pathogenesis of Alzheimer’S disease(AD). Methods Male SAMP8 mice of 10-month old were taken as animal model of AD and SAMR1 mice were taken as control group. Morris water maze(MWM), electron microscope and western blotting were used in this study. Results Comparing with the control group, the model group had significant learning impairment and memory retention deficits. The thickness of post synaptic density(PSD) and the curvature of the synaptic interface in the model group dicrease. The width of synaptic cleft in the model group increased. The expression of GluR2 in the model group dicreased. There were no significant differences in the expression of GluR1 between two groups. Conclusions Impaired synaptic plasticity mediated by pathological alteration of AMPA receptor in hippocampus mey be the pathogenesis underlying learning and memory disorders of AD.

Key words: Senescence accelerated mouse prone 8, Alzheimer’s disease, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, Synaptic plasticity, Learning , and memory, Morris water maze, Western blotting, Mouse