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 张英俊 鲁娟 熊殷艺 吴巧凤 于美玲 卢圣锋 余曙光*

解剖学报 ›› 2014, Vol. 45 ›› Issue (1) : 15-19.

欢迎访问《解剖学报》官方网站!今天是 English
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

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*
作者信息 +

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*
Author information +
文章历史 +

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。

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.

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

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

引用本文

导出引用
封敏 张英俊 鲁娟 熊殷艺 吴巧凤 于美玲 卢圣锋 余曙光*. 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[J]. 解剖学报. 2014, 45(1): 15-19 https://doi.org/10.3969/j.issn.0529-1356.2014.01.003
FENG Min ZHANG Ying-jun LU Juan XIONG Yin-yi WU Qiao-feng YU Mei-ling LU Sheng-feng YU Shu-guang*. Abnormal expression of AMPA receptor in hippocampus of senescence accelerated mouse prone 8 correlated to synaptic plasticity[J]. Acta Anatomica Sinica. 2014, 45(1): 15-19 https://doi.org/10.3969/j.issn.0529-1356.2014.01.003

参考文献

[1]Newpher TM, Ehlers MD. Glutamate receptor dynamics in dendritic microdomains[J]. Neuron,2008,58(4):472-497.
[2]Helmut WK,Roberto M. Synaptic AMPA receptor plasticity and behavior[J]. Neuron, 2009,61(3):340-350.
[3]Ikonomovic MD, Mizukami K, Davies P, et al.The loss of GluR2(3) immunoreactivity precedes neurofibrillary tangle formation in the entorhinal cortex and hippocampus of Alzheimer brains[J]. J Neuropathol Exp Neurol,1997,56(9):1018-1027.
[4]Zhao WQ, Santini F, Breese R,et al. Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors prevents amyloid beta oligomer-induced synaptic disruption[J].J Biol Chem,2010,285(10):7619-7632.
[5]Morley JE, Farr SA, Kumar VB, et al. The SAMP8 mouse: a nodel to develop therapeutic  interventions for Alzheimer’s disease[J].Curr Pharm Des,2012,18(8):1123-1130.
[6]Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory[J].Nat Protoc,2006,1(2):848-858.
[7]Jones DG, Calverley RK. Frequency of occurrence of perforated synapses in developing rat neocortex [J].Neurosci Lett,1991, 129( 2):189-192.
[8]Jones DG, Devon RM. An uhrastructural study into the effect of pentobarbition on synaptic organization[J].Brain Res,1978,147(1):47-63.
[9]Takeda T, Hosokawa M, Higuchi K. Senescence-accelerated mouse (SAM): a novel murine model of senescence[J]. Exp Gerontol, 1997,32(12):105-109.
[10]Takahashi R. Anti-aging studies on the senescence accelerated mouse (SAM) strains [J]. Yakugaku Zasshi,2010,130(1):11-18.( in Japanese)
[11]Pallas M, Camins A, Smith MA, et al. From aging to Alzheimer’s disease: unveiling “the switch” with the senescence-accelerated mouse model (SAMP8) [J].J Alzheimers Dis, 2008,15(4):615-624.
[12]Cui HX,Li Sh,Gu P,et al. Effects of androgen on learning and memory ability and hippocampus neurons in SAMP8 mouse [J]. Acta Anatomica Sinica, 2008,39(3):365-369.(in Chinese)
崔慧先;李莎;顾平,等.雄激素对SAMP8小鼠学习记忆能力及海马神经元的影响[J].解剖学报, 2008,39(3):365-369. 
[13]Cui HX, Xie GSh, Li Sh, et al. Effects of dihydrotestosterone on synaptic plasticity and the expression of N-methyl-D-aspartate receptor 1 in CA1 region of hippocampus in SAMP8 mouse [J]. Acta Anatomica Sinica, 2010,41(6):809-813. (in Chinese)
崔慧先,解国圣,李莎,等.双氢睾酮对快速老化小鼠海马CAl区突触可塑性和N-甲基-D-天冬氨酸受体1的影响[J]. 解剖学报,2010,41(6):809-813.
[14]Isaac JT, Ashby MC, McBain CJ. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity[J]. Neuron,2007,54(6):859-871.
[15]Savtchouk I, Liu SJ. Remodeling of synaptic AMPA receptor subtype alters the probability and pattern of action potential firing[J]. J Neurosci, 2011,31(2): 501-511.
[16]Parameshwaran K, Dhanasekaran M, Suppiramaniam V. Amyloid beta peptides and glutamatergic synaptic dysregulation[J]. Exp Neurol, 2008, 210(1): 7-13.
[17]Liang Z, Liu F, Iqbal K, et al. Dysregulation of tau phosphoryla-tion in mouse brain during excitotoxic damage[J]. J Alzheimers Dis, 2009, 17(3):531-539.
[18]Small SA, Perera GM, DeLaPaz R, et al. Differential regional dysfunction of the hippocampal formation amongelderly with memory decline and Alzheimer’s disease[J]. Ann Neurol,1999, 45(4):466-472.
[19]Craig AM, Blackstone CD, Huganir RL, et al. The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits[J]. Neuron,1993,10(6):1055-1068.
[20]Jayakar SS, Dikshit M.AMPA receptor regulation mechanisms: future target for safer neuroprotective drugs[J].Int J Neurosci,2004,114(6):695-734.
 

基金

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


Accesses

Citation

Detail

段落导航
相关文章

/