卒中后认知障碍小鼠胆碱能神经环路组蛋白乙酰化内稳态失衡的机制研究

被引：10

作者：

王鑫

孙彩花

徐旸

朱小云

陈霞

施伟

杨敏

机构：

[1] 扬州大学医学院附属江苏省扬州五台山医院神经康复科

来源：

中国康复理论与实践 | 2016年 / 06期

关键词：

卒中后认知障碍; 胆碱能环路; 乙酰胆碱; 组蛋白乙酰化; cAMP反应元件结合蛋白; 小鼠;

D O I：

暂无

中图分类号：

R749.1 [脑器质性精神障碍];

学科分类号：

100205 ;

摘要：

目的观察卒中后认知障碍小鼠胆碱能神经环路组蛋白乙酰化内稳态变化。方法选用清洁级ICR雄性小鼠分为假手术组(n=60)和卒中后认知障碍组(PSCI组,n=60)。采用线栓法制备大脑中动脉栓塞(MCAO)模型。水迷宫测试检测小鼠认知功能;分子生物学等方法检测小鼠梗死对侧胆碱能神经环路功能和组蛋白乙酰化内稳态变化情况。结果与假手术组相比,PSCI组水迷宫成绩下降(t>29.412,P<0.05);中枢胆碱能神经环路中,乙酰胆碱(ACh)的含量降低(t>26.227,P<0.05),胆碱乙酰基转移酶(Ch AT)m RNA和蛋白的表达降低(t>28.593,P<0.05),乙酰化组蛋白H3(Ac-H3)水平降低(t>24.126,P<0.05),磷酸化c AMP反应元件结合蛋白(p-CREB)和CREB结合蛋白(CBP)表达降低(t>25.634,P<0.05),Ch AT基因M型启动子组蛋白乙酰化水平下降(t>24.704,P<0.05)。结论短暂性MCAO模型可以引起小鼠认知功能障碍。PSCI小鼠中枢胆碱能神经环路的胆碱能系统功能受损,乙酰化内稳态失衡,Ch AT基因启动子组蛋白乙酰化程度下降;这些很可能与脑卒中导致环路中相应脑区中p-CREB和CBP表达降低有关。

引用

页码：621 / 628

页数：8

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