Effects of small interfering RNA targeting sphingosine kinase-1 gene on the animal model of Alzheimer’s disease
Effects of small interfering RNA targeting sphingosine kinase-1 gene on the animal model of Alzheimer’s disease
复制标题
鞘氨醇激酶1基因小干扰RNA对阿尔茨海默病动物模型的影响
DOI：
10.1007/s11596-013-1136-5
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Sheng
中科院分区：
文献类型：
--
作者：
Yuan Zhang 张 远;Qian Yu 禹 虔;Tian;Yang Yang 杨 阳;G. 刚;Sheng
阿尔茨海默病（AD）是一种与年龄相关的渐进性神经退行性疾病，其逐渐发生并导致记忆、行为和人格改变。以往曾有AD患者鞘脂代谢异常的报道。本研究旨在通过siRNA干扰方法，探讨ADPK 1是否能促进AD动物模型中淀粉样蛋白（Aβ）的积累，增强其学习记忆能力。设计表达针对APPK 1基因的小干扰RNA（siRNA）的腺病毒载体（APPK 1-siRNA），并在用APPK 1-siRNA海马注射治疗后4周检查APPK 1-siRNA对APP/PS1小鼠的影响。SphK 1蛋白表达通过使用Western印迹法确认，神经酰胺含量与S1 P分泌通过酶联免疫吸附试验（ELISA）进行评价。免疫组化染色和ELISA法检测Aβ含量。采用Morris水迷宫检测APP/PS 1小鼠的学习记忆能力。siRNA组与对照组相比，PDK 1蛋白和mRNA的表达差异有统计学意义（P < 0. 05）。体内实验表明，转染后小鼠Aβ负荷明显增加，学习记忆能力明显增强。AD动物模型中的Aβ负荷和学习记忆能力可能对AD的治疗有重要意义。
Alzheimer’s disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. Abnormal sphingolipid metabolism was reported in AD previously. This study aimed to investigate whether sphK1 could exacerbate the accumulation of amyloid protein (Aβ) and sharpen the learning and memory ability of the animal model of AD using siRNA interference. An adenovirus vector expressing small interfering RNA (siRNA) against the sphK1 gene (sphK1-siRNA) was designed, and the effects of sphK1-siRNA on the APP/PS1 mouse four weeks after treatment with sphK1-siRNA hippocampal injection were examined. SphK1 protein expression was confirmed by using Western blotting and ceramide content coupled with S1P secretion was evaluated by enzyme-linked immunosorbent assay (ELISA). Aβ load was detected by immunohistochemical staining and ELISA. Morris water maze was adopted to test the learning and memory ability of the APP/PS1 mice. A significant difference in the expression of sphK1 protein and mRNA was observed between the siRNA group and the control group. Aβ load in transfected mice was accelerated in vivo, with significant aggravation of the learning and memory ability. The sphK1 gene modulation in the Aβ load and the learning and memory ability in the animal model of AD may be important for the treatment of AD.
影响因子：
120.7
作者：
Näslund, J;Haroutunian, V;Buxbaum, JD
通讯作者：
Buxbaum, JD
DOI：
--
发表时间：
2003
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
L. Puglielli;Blake C. Ellis;A. Saunders;D. Kovacs
通讯作者：
L. Puglielli;Blake C. Ellis;A. Saunders;D. Kovacs