阿尔茨海默病与野生型小鼠海马中CREB1活性差异研究
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国家自然科学青年基金项目(81401095);湖北省卫生计生青年人才项目(WJ2015Q045);长江大学青年人才基金项目(2015cqr24)


Activity of CREB1 in the hippocampus of Alzheimer’s disease and wild type mice
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    摘要:

    目的:检测阿尔茨海默病(Alzhemer’s disease,AD)和野生型对照组小鼠海马CREB1蛋白的活性及意义-方法:D-半乳糖90 mg/(kg·d)联合三氯化铝(AlCl3)40 mg/(kg·d)连续90 d腹腔注射制造AD小鼠模型;通过糖水偏好实验及Y-迷宫实验初步鉴定模型复制成功;免疫组化检测-比较AD及野生型对照组小鼠海马CA1-CA3和DG区CREB1和p-CREB1蛋白表达水平-结果:与对照组比较,AD模型组小鼠糖水偏好百分比明显下降(P < 0.01)-AD组小鼠对新异臂的空间辨别能力明显低于野生型对照组(P﹤0.01)-与野生型对照组相比,AD小鼠海马CA1-CA3和DG区CREB1-p-CREB1蛋白阳性表达强度低,阳性颗粒数目少(P﹤0.01)-结论:D-半乳糖联合AlCl3通过抑制海马组织关键核转录因子CREB1的活性,影响神经元的存活-损伤后的修复及神经细胞再生,导致小鼠学习记忆能力受损,进而引起AD的发生-发展-

    Abstract:

    Objective:To detect, compare and analyze the activity and significance of CREB1 protein in the hippocampus of Alzheimer’s disease (AD) and wild type control mice. Methods:Continuous intraperitoneal injection of D-galactose 90 mg/(kg·d) and AlCl3 40 mg/(kg·d) for 90 days was performed to mice to make AD mouse model. Preliminary appraise of AD model was performed by sucrose preference test and Y-maze test. CREB1, p-CREB1 protein expression levels in the hippocampal CA1, CA3 and DG areas of AD and wild type control mice were compared by immunohistochemical detection, respectively. Results:Compared with the control group, the sucrose preference percentage of AD mice decreased significantly (P < 0.01). The spatial discrimination ability of the AD group was significantly lower than that of the wild-type control group (P < 0.01). Compared with the wild type control group, the positive expressions of CREB1 and p-CREB1 proteins in the hippocampal CA1, CA3 and DG areas were significantly decreased in AD mice (P < 0.01). Conclusion:By inhibiting the activity of key nuclear transcription factor CREB1 in hippocampal tissues, D-galactose combined with AlCl3 affect neuronal survival, post injury repair and regeneration of nerve cells, resulting in ability of learning and memory impaired, thereby causing the occurrence and development of AD.

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王 玲,李先发,陈 蒙,王 谦,杨 群,苏 波,刘 洋.阿尔茨海默病与野生型小鼠海马中CREB1活性差异研究[J].南京医科大学学报(自然科学版),2016,(8):956-959

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  • 收稿日期:2016-02-01
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  • 在线发布日期: 2016-08-19
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