【摘要】：阿爾茨海默癥(AD)是最普遍的一種以進(jìn)行性認(rèn)知障礙和記憶力損害為主的中樞神經(jīng)系統(tǒng)退行性疾病。本實驗中利用前腦條件性早老素基因1和早老素基因2雙敲除cDKO小鼠作為實驗動物模型,研究探討使用組蛋白去乙�；敢种苿┒∷徕c對cDKO模型小鼠記憶改善的長期作用以及對大腦神經(jīng)細(xì)胞再生的影響。 在前期研究中,本實驗組已經(jīng)證實了連續(xù)21天給予組蛋白去乙�；敢种苿┒∷徕c,可以顯著改善小鼠記憶功能和前腦神經(jīng)退行性病變表型。為了進(jìn)一步研究這種作用的深層機制,我們研究了丁酸鈉對成熟神經(jīng)細(xì)胞再生的影響,發(fā)現(xiàn)丁酸鈉確實能顯著提高cDKO小鼠海馬DG區(qū)域的神經(jīng)細(xì)胞再生。但是,丁酸鈉對記憶功能以及神經(jīng)細(xì)胞再生的影響被證明是短暫的。用藥21天并停藥1個月之后,我們檢測了小鼠的條件性恐懼記憶功能。和我們之前用藥后立即檢測記憶水平所得到的結(jié)果不同,我們發(fā)現(xiàn)cDKO小鼠的記憶與未給藥的控制組相比沒有顯著的提高。而且,在海馬DG區(qū),神經(jīng)細(xì)胞的再生也沒有顯著的增加。這些結(jié)果顯示,即使組蛋白去乙�；缚梢宰鳛橹委烝D的潛在靶點,但是持續(xù)的用藥還是必需的。
[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.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R749.16

【共引文獻(xiàn)】

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本文編號：2178475