利用早老素PS1-PS2双敲除小鼠研究组蛋白乙酰化对神经退行性病变的调控作用
发布时间：2018-08-12 08:16
【摘要】：阿尔茨海默症(AD)是最普遍的一种以进行性认知障碍和记忆力损害为主的中枢神经系统退行性疾病。本实验中利用前脑条件性早老素基因1和早老素基因2双敲除cDKO小鼠作为实验动物模型,研究探讨使用组蛋白去乙酰化酶抑制剂丁酸钠对cDKO模型小鼠记忆改善的长期作用以及对大脑神经细胞再生的影响。 在前期研究中,本实验组已经证实了连续21天给予组蛋白去乙酰化酶抑制剂丁酸钠,可以显著改善小鼠记忆功能和前脑神经退行性病变表型。为了进一步研究这种作用的深层机制,我们研究了丁酸钠对成熟神经细胞再生的影响,发现丁酸钠确实能显著提高cDKO小鼠海马DG区域的神经细胞再生。但是,丁酸钠对记忆功能以及神经细胞再生的影响被证明是短暂的。用药21天并停药1个月之后,我们检测了小鼠的条件性恐惧记忆功能。和我们之前用药后立即检测记忆水平所得到的结果不同,我们发现cDKO小鼠的记忆与未给药的控制组相比没有显著的提高。而且,在海马DG区,神经细胞的再生也没有显著的增加。这些结果显示,即使组蛋白去乙酰化酶可以作为治疗AD的潜在靶点,但是持续的用药还是必需的。
[Abstract]:Alzheimer's disease (AD) is the most common central nervous system degenerative disease characterized by progressive cognitive impairment and memory impairment. In this experiment, the cDKO mice were used as the experimental animal model with the double knockout of presbycin gene 1 and presenin gene 2 in the forebrain. To investigate the long-term effect of sodium butyrate, a histone deacetylase inhibitor, on memory improvement and regeneration of neural cells in cDKO model mice. In previous studies, it has been proved that sodium butyrate, a histone deacetylase inhibitor, can significantly improve the memory function and the phenotype of anterior neurodegenerative lesions in mice after 21 days of continuous administration of sodium butyrate, an inhibitor of histone deacetylase. In order to further study the deep mechanism of this effect, we studied the effect of sodium butyrate on the regeneration of mature nerve cells. It was found that sodium butyrate could significantly increase the regeneration of neurons in the DG region of hippocampus of cDKO mice. However, the effects of sodium butyrate on memory and nerve cell regeneration have been shown to be short-lived. After 21 days and 1 month of withdrawal, we tested the conditioned fear memory function in mice. In contrast to the results we obtained immediately after administration of the drug, we found no significant improvement in memory in cDKO mice compared with the unadministered control group. Moreover, there was no significant increase in nerve cell regeneration in the DG region of the hippocampus. These results suggest that, even if histone deacetylase is a potential target for AD, continued medication is necessary.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16
本文编号：2178475
[Abstract]:Alzheimer's disease (AD) is the most common central nervous system degenerative disease characterized by progressive cognitive impairment and memory impairment. In this experiment, the cDKO mice were used as the experimental animal model with the double knockout of presbycin gene 1 and presenin gene 2 in the forebrain. To investigate the long-term effect of sodium butyrate, a histone deacetylase inhibitor, on memory improvement and regeneration of neural cells in cDKO model mice. In previous studies, it has been proved that sodium butyrate, a histone deacetylase inhibitor, can significantly improve the memory function and the phenotype of anterior neurodegenerative lesions in mice after 21 days of continuous administration of sodium butyrate, an inhibitor of histone deacetylase. In order to further study the deep mechanism of this effect, we studied the effect of sodium butyrate on the regeneration of mature nerve cells. It was found that sodium butyrate could significantly increase the regeneration of neurons in the DG region of hippocampus of cDKO mice. However, the effects of sodium butyrate on memory and nerve cell regeneration have been shown to be short-lived. After 21 days and 1 month of withdrawal, we tested the conditioned fear memory function in mice. In contrast to the results we obtained immediately after administration of the drug, we found no significant improvement in memory in cDKO mice compared with the unadministered control group. Moreover, there was no significant increase in nerve cell regeneration in the DG region of the hippocampus. These results suggest that, even if histone deacetylase is a potential target for AD, continued medication is necessary.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16
【共引文献】
相关期刊论文 前2条
1 陈涛;田增民;杜亚楠;;神经干细胞移植途径的理论研究进展[J];中国组织工程研究与临床康复;2009年40期
2 牟大鹏;苏冠方;徐春玲;王世瑶;王心蕊;;骨髓间充质干细胞向视网膜神经节样细胞的诱导分化[J];眼科新进展;2009年02期
相关博士学位论文 前1条
1 朱宁喜;动眼神经损伤后神经再生和电刺激对其作用的研究[D];山东大学;2009年
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