期刊文献+

β-淀粉样蛋白和drebrin在培养的APP/PS1转基因小鼠神经元中的表达 被引量:2

Expressions of β-amyloid protein and drebrin in cultured neurons of the APP/PS1 transgenic mouse
下载PDF
导出
摘要 目的: 探讨阿尔茨海默病(AD)脑内β-淀粉样蛋白(Aβ)积聚与树突棘蛋白drebrin表达变化之间的关系.方法: 采用免疫细胞化学、ELISA和免疫印迹法等方法检测大脑皮层原代培养的APP/PS1转基因小鼠的神经元和同种野生型(WT)小鼠的神经元Aβ和drebrin的表达.结果: 培养至12d (days in vitro)时,可见Aβ在APP/PS1神经元胞体内聚集,培养基内的Aβ水平也同时升高;此期神经元内drebrin斑点状免疫反应产物分布较为稀疏,drebrin的表达水平下降.18d时,Aβ在胞体内聚集的基础上,向突起内延伸,培养基内的Aβ水平进一步升高;drebrin的表达则明显下降.结论: 原代培养的APP/PS1小鼠神经元内Aβ积聚的同时,树突棘蛋白drebrin的表达下降.提示AD脑内Aβ积聚可能是影响树突棘蛋白drebrin表达的因素之一. Objective: To investigate the relationship between β-amyloid protein (Aβ) accumulation and the expression change of the dendritic spine protein drebrin in the brain of Alzheimer's disease (AD). Methods: The expressions of Aβ and drebrin in primary cultured neurons from the cerebral cortex of the APP/PS1 transgenic and wild type mice by means of immunocy- tochemistry, ELISA and Western blotting. Results: Compared with control neurons from the wild type mice, the Aβ was observed to be gathered in perikarya of the neurons of the APP/PS1 transgenic mice and the Aβ level was increased in the same time in culture medium at 12 days in vitro ; meanwhile, the irnmunoreactive spot of the drebrin was rarely seen, the ex- pression level of drebrin was decreased. In 18 d in vitro, the pericaryon gathered Aβ was observed to be spread into the processes, and the Aβ level in the culture medium was obviously increased; the expression level of drebrin was significantly decreased. Conclusion: These results indicated that accumulation of the Aβin the primary cultured APP/PS1 neurons followed by a decreased expression of the drebrin, which suggested that Aβ accumulation might be one of the reasons of decrease of the drehrin in the brain of AD.
出处 《解剖学杂志》 CAS CSCD 北大核心 2010年第4期502-505,F0002,共5页 Chinese Journal of Anatomy
基金 受安徽省高校优秀青年人才基金(2010SQRL125)部分资助
关键词 Β-淀粉样蛋白 DREBRIN 阿尔茨海默病 APP/PS1 转基因 神经元 原代培养 β-amyloid protein drebrin Alzheimer's disease APP/PS1 transgenic neuron primary culture
  • 相关文献

参考文献15

  • 1Aoki C,Sekino Y,Hanamura K,et al.Drebrin A is a postsynaptic protein that localizes in vivo to the submembranous surface of dendritic sites forming excitatory synapses[J].J Comp Neurol,2005,483(4):383-402.
  • 2Harigaya Y,Shoji M,Shirao T,et al.Disappearance of actin-binding protein,drebrin,from hippocampal synapses in Alzheimers disease[J].J Neurosci Res,1996,43(1):87-92.
  • 3Hatanpaa K,Isaacs K R,Shirao T,et al.Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease[J].J Neuropathol Exp Neurol,1999,58(6):637-643.
  • 4Jeffery M C,Watterson D M,Linda J V.Human amyloid β-induced neuroinflammation is an early event in neurodegeneration[J].Glia,2006,53(5):484-490.
  • 5Jankowsky J L,Fadale D J,Anderson J,et al.Mutant presenilins specifically elevate the levels of the Aβ 42 residue β-amyloid peptide in vivo:evidence for augmentation of Aβ 42-specific γ secretase[J].Human Mol Genetics,2004,13(2):159-170.
  • 6姚君茹,高璐,于剑锋,柴继侠,王月华,马丽香,陈祖林,李瑞锡,彭裕文.p21活化激酶在APP/PS1转基因AD小鼠模型海马内表达的年龄变化(英文)[J].神经解剖学杂志,2008,24(1):1-7. 被引量:6
  • 7Takahashi R H,Almeida C G,Kearney P F,et al.Oligomerization of Alzheimers beta-amyloid within processes and synapses of cultured neurons and brain[J].J Neurosci,2004,24(14):3592-3599.
  • 8Runz H,Rietdorf J,Tomic I,et al.Inhibition of intracellular cholesterol transport alters resenilin localization and amyloid precursor protein processing in neuronal cells[J].J Neurosci,2002,22(5):1679-1689.
  • 9Fang B Y,Ha L F,Jia H P.Chinese Presenilin-1 V97L mutation enhanced A beta 42 levels in SH-SY5Y neuroblastoma cells[J].Neurosci Lett,2006,406(1-2):33-37.
  • 10Oddo S,Caccamo A,Shepherd J D,et al.Triple-transgenic model of Alzheimers disease with plaques and tangles:intracellular Aβ and synaptic dysfunction[J].Neuron,2003,39(3):409-421.

二级参考文献1

共引文献5

同被引文献16

  • 1张赛圣,程丽霞,吕诚.肌动蛋白结合蛋白在神经元树突棘重塑中的作用[J].中国老年学杂志,2014,34(6):1688-1690. 被引量:1
  • 2Wang WY,Tan MS,Yu JT,et al.Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease[J].Ann Transl Med,2015;3(10):136.
  • 3Rao JS,Kellom M,Kim HW,et al.Neuroinflammation and synaptic loss[J].Neurochem Res,2012;37(5):903-10.
  • 4Zheng Y,Zhang WJ,Wang XM.Triptolide with potential medicinal value for diseases of the central nervous system[J].CNS Neurosci Ther,2013;19(2):76-82.
  • 5Wang Q,Xiao B,Cui S,et al.Triptolide treatment reduces Alzheimer's disease(AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD[J].Dis Model Mech,2014;7(12):1385-95.
  • 6Wan B,Hu X,Nie J,et al.Effects of triptolide on degeneration of dendritic spines induced by Aβ1~40injection in rat hippocampus[J].Neurol Sci,2014;35(1):35-40.
  • 7Hayashi K,Shirao T.Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons[J].J Neurosci,1999;19(10):3918-25.
  • 8Takahashi H,Mizui T,Shirao T.Down-regulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurones[J].J Neurochem,2006;97(1):110-5.
  • 9Gong X,Lu X,Zhan L,et al.Role of the SNK-SPAR pathway in the development of Alzheimer's disease[J].IUBMB Life,2010;62(3):214-21.
  • 10Mahadomrongkul V,Huerta PT,Shirao T,et al.Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PS1 genes[J].Brain Res,2005;1064(1-2):66-74.

引证文献2

二级引证文献6

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部