摘要
目的研究β-淀粉样蛋白(Aβ1~42)对大鼠大脑神经型尼古丁受体α7亚单位表达及学习记忆能力的影响,探讨这些改变在阿尔茨海默病(AD)发病机制中的作用。方法用立体定向法将Aβ1~42(1mg/ml,5μl)注入Wistar大鼠侧脑室,用免疫组化方法测定大鼠大脑中Aβ1~42的沉积,用Western印迹法和RT-PCR方法分别测定神经型尼古丁受体α7亚单位在蛋白和基因水平的表达,用水迷宫法检测大鼠的学习记忆能力。结果与对照组比较,经Aβ1~42侧脑室注射后的大鼠大脑皮层出现明显Aβ1~42沉积;神经型尼古丁受体α7亚单位蛋白质表达水平明显降低;α7亚单位mRNA表达水平明显升高;大鼠学习记忆能力明显降低。结论Aβ1~42引起神经型尼古丁受体α7亚单位的表达明显改变,并导致大鼠学习记忆力降低,可能是AD发病机制中的重要因素。
Objective To study the effect of β-amyloid protein ( Aβ1 -42 ) on the expression of α7 subunits of nicotinic acetylcoline receptors (nAChRs) and the ability of learning and memory of rats to explore the roles of these changes in pathogenesis of Alzheimer's disease (AD). Methods Aβ1 -42 ( 1 mg/ml,5 μl) was injected into the second ventricle of cerebrum of rats by stereotaxis method. The deposi- tion of Aβ1 -42 was detected by immunohisitochemistry. The expressions of α7 subunits of nAChRs at protein and mRNA levels were measured by Western blotting and RT-PCR respectively and the ability of learning and memory of rats was detected by the Morris water maze. Results The deposition of Aβ1 -42 in the cortex of rat brain injected by Aβ1 -42 was obviously observed. Injection of Aβ1 -42 decreased the expression of α7 subunits of nAChRs at protein level. At the mRNA level, upregulated expression of α7 nAChRs was found. Injected Aβ resulted in reduction of learning and memory of rats. Conclusions Aβ1-42 can significantly influence the expressions of α7 nAChR subunits in brain ,and reduce the ability of learning and memory of rats,which may play an important role in the pathogenesis of AD.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2007年第19期1860-1862,共3页
Chinese Journal of Gerontology
基金
国家自然科学基金资助项目(30460045)
科技部国际合作基金资助项目(2004DFB02800)
贵州省科研基金(S2006-1
D2006-2)
关键词
Β-淀粉样蛋白
神经型尼古丁受体
学习记忆
大鼠
β-amyloid protein(Aβ)
Nicotinic acetylcoline receptors
Learning and memory
Rats