杏仁核注射Aβ_(25-35)后大鼠脑内细胞周期蛋白、tau蛋白和Bax蛋白的异常表达  

Aberrant neuronal expression of mitotic protein, tau and Bax in the rat brain after injection of Aβ_(25-35) into the amygdala

作　　者：洪道俊[1] 裴爱琳[1] 孙凤艳[1] 朱粹青[1] 

机构地区：[1]复旦大学上海医学院医学神经生物国家重点实验室,上海200032

出　　处：《生理学报》2003年第2期142-146,共5页Acta Physiologica Sinica

基　　金：ThisworksupportedbytheNationalNaturalScienceFoundationofChina ( 739830 45 0 ) ;973Program (G19990 5 40 0 ) ;andEducationalFounda tionofChina ( 2 0 0 0 66)

摘　　要：近年来研究发现 ,阿尔茨海默病 (Alzheimer′sdisease ,AD)病人脑内神经元细胞周期相关蛋白的异常表达与AD相关病理改变存在关联。为探讨 β 淀粉样蛋白 ( β amyloid ,Aβ)的毒性作用能否导致成年脑神经元表达细胞周期相关蛋白 ,以及细胞周期相关蛋白表达与神经损伤之间的关系 ,我们运用免疫组化、积分光密度分析等方法对Aβ2 5 35多肽片段单侧杏仁核注射的大鼠脑进行了研究。结果显示 ,Aβ2 5 35注射的大鼠脑内除了有与神经纤维缠结相关的磷酸化tau蛋白和凋亡相关蛋白Bax蛋白水平增加外 ,术后 7d细胞周期相关蛋白cyclinA和cyclinB1蛋白在神经元内异常表达 ,但术后 2 1d时cyclinA的表达有所降低 ,而cyclinB1在脑内神经元中已检测不到 ;免疫荧光双标结果显示Aβ2 5 35注射后 7d的大鼠脑内有较多的cyclinB1和Bax、cyclinB1和磷酸化tau蛋白共存的神经元 ,而Bax与磷酸化tau蛋白阳性信号很少共存在同一细胞上。以上结果提示 ,Aβ可导致成年脑神经元表达细胞周期相关蛋白 ,这些神经元可能会通过与Bax相关的凋亡途径死亡 。Recent evidence indicates that the aberrant neuronal expression of mitotic proteins in Alzheimer′s disease (AD) brain may be related to AD pathological changes. To investigate whether the toxicity of β-amyloid protein (Aβ) induces mitotic proteins expression in adult rat brain, we used immunohistochemical and integral optical density analytic method to analyze the adult rat brains, which had been injected with Aβ 25-35 into unilateral amygdala. Results showed that the levels of neurofibrillary tangle (NFT) related phosphorylated tau protein and apoptosis related protein Bax were increased in Aβ 25-35 injected rat brains, meanwhile the aberrantly expression of mitotic protein cyclin A and cyclin B1 was also detected at 7 d after operation, but the level of cyclin A decreased and cyclin B1 disappeared at 21 d. Immunofluorescence double labeling presented that cyclin B1 was partially co-localized with Bax or phosphorylated tau protein, whereas Bax and phosphorylated tau protein seldom co-localized. These results suggest that Aβ causes mitotic protein expression in adult brain neurons, which may die through apoptosis or may be affected by AD NFT-related tau phosphorylation.

关 键 词：脑 β-淀粉样蛋白 CYCLIN A CYCLIN B1 TAU蛋白 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学]