甜菜碱逆转同型半胱氨酸引起的阿尔茨海默样病理改变及记忆损伤

发布时间：2018-06-14 20:29

本文选题：阿尔茨海默病 + 同型半胱氨酸　；参考：《华中科技大学》2013年硕士论文

【摘要】：阿尔茨海默病（Alzheimer’s disease，AD)是一种最常见的神经退行性疾病，其病理学特征为：神经原纤维缠结（neurofibrillary tangles，NTFs）和老年斑（senileplaque，SP）。同型半胱氨酸（homocysteine，Hcy）血浆浓度升高可以引起Tau蛋白过度磷酸化和Aβ积累，造成记忆损伤。同时给予叶酸和维生素B12可以降低血浆中同型半胱氨酸的浓度，降低同型半胱氨酸造成的Tau蛋白过度磷酸化，减少Aβ沉积，逆转记忆损伤。但是在一些亚甲基四氢叶酸还原酶突变的人群中，叶酸和维生素B12不能改善体内的高同型半胱氨酸。甜菜碱可以通过甜菜碱-同型半胱氨酸甲基转移酶来提供甲基，促进同型半胱氨酸的代谢，但是否可以改善同型半胱氨酸造成的阿尔茨海默样病变和记忆损伤尚不清楚。方法：通过给予大鼠尾静脉注射同型半胱氨酸2周，造成高同型半胱氨酸模型，在饮水中同时给予甜菜碱来探究甜菜碱的逆转作用。造模成功的大鼠通过水迷宫检测学习记忆能力、通过电生理记录LTP的变化、通过高尔基染色检测神经元树突的变化、通过免疫印迹、免疫组织化学检测Tau蛋白磷酸化水平及记忆相关蛋白水平、通过酶联免疫吸附检测Aβ的沉积。结果：通过研究，，我们发现同时给予甜菜碱可以逆转同型半胱氨酸的影响，改善记忆损伤，增强LTP，增加树突分支数目和树突棘密度，上调NR1、NR2A、突触结合蛋白、突触泡蛋白、磷酸化的突触蛋白I的含量，通过降低PP2AC309位点去甲基化、307位点磷酸化水平来激活PP2AC，从而降低Tau蛋白位点中与阿尔茨海默相关的磷酸化水平，通过降低PS-1的含量，从而降低Aβ沉积。结论：通过上述实验结果，证明甜菜碱可以逆转同型半胱氨酸引起的阿尔茨海默样病理改变及记忆损伤。
[Abstract]:Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Its pathological features are neurofibrillary tangles (NTFs) and senileplaqueus (SPF). The increase of homocysteine (Hcyine) plasma concentration can induce the excessive phosphorylation of Tau protein and the accumulation of A 尾, resulting in memory impairment. At the same time, folic acid and vitamin B12 could decrease the concentration of homocysteine in plasma, decrease the excessive phosphorylation of Tau protein induced by homocysteine, reduce A 尾 deposition and reverse memory impairment. However, in some populations with methylene tetrahydrofolate reductase mutation, folic acid and vitamin B12 did not improve homocysteine levels in the body. Betaine can provide methyl-homocysteine methyltransferase to promote the metabolism of homocysteine, but it is not clear whether it can improve Alzheimer's disease and memory impairment caused by homocysteine. Methods: the model of hyperhomocysteine was established by injecting homocysteine into rat tail vein for 2 weeks, and the reversal effect of betaine was investigated by taking betaine in drinking water at the same time. Successful rats were tested for learning and memory by water maze, LTP by electrophysiology, dendrites by Golgi staining, and immunoblotting by immunoblotting. The levels of Tau protein phosphorylation and memory-related proteins were detected by immunohistochemistry, and A 尾 deposition was detected by enzyme-linked immunosorbent assay (Elisa). Results: we found that simultaneous administration of betaine could reverse the effects of homocysteine, improve memory impairment, enhance LTP, increase the number of dendritic branches and dendritic spine density, upregulate NR1 + NR2A, synaptophysin, synaptic vesicle protein. Phosphorylated synaptophysin I activates PP2AC307 by lowering the phosphorylation level at PP2AC309, thereby reducing the Alzheimer associated phosphorylation at Tau, and PS-1 by reducing PS-1. Thus, A 尾 deposition was reduced. Conclusion: these results suggest that betaine can reverse Alzheimer's like pathological changes and memory impairment induced by homocysteine.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16

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