膳食GM1对AD小鼠神经节苷脂代谢的调控作用

Dietary GM1 Modulates Metabolism of Gangliosides in AD Mice

为探究外源单唾液酸四己糖神经节苷脂(monosialotetrahexosyl ganglioside,GM1)对阿尔兹海默症(Alzheimer’s disease,AD)小鼠内源性神经节苷脂(gangliosides,GLS)代谢的调控作用。采用淀粉样蛋白和人早老蛋白1(APPswe/PSEN1dE9,APP/PS1)双转基因小鼠作为AD模型,首先利用Morris水迷宫观测摄食GM1对APP/PS1小鼠行为学的影响;进而利用液相色谱-质谱法(liquid chromatography-mass spectrometry,LC-MS)分析GM1对APP/PS1小鼠脑皮质中GLS总体水平及各亚类水平的影响,采用多元统计分析探究GLS分子种变化。最后利用实时荧光定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测GLS合成与分解基因的mRNA表达。结果表明,GM1能够改善APP/PS1小鼠的空间学习与记忆能力、提高脑皮质中GLS总含量、回调APP/PS1小鼠脑皮质中GLS各亚类含量。摄食GM1能够显著上调GLS合成基因(st3gal5p1、st8sia1、b3galt4、st3gal2和soat)的mRNA表达水平,下调GLS分解基因hexa的mRNA表达水平。综上,膳食GM1可以调控AD小鼠脑内GLS的代谢。

The regulatory effect of exogenous monosialotetrahexosyl ganglioside(GM1)on the metabolism of endogenous gangliosides(GLS)was investigated in the Alzheimer's disease(AD)model established with APPswe/PSEN1dE9(APP/PS1)double transgenic mice.Morris water maze was designed to examine the behaviors of the APP/PS1 mice.Further,liquid chromatography-mass spectrometry(LC-MS)was employed to measure the overall level of GLS and the level of each subclass in the cerebral cortex of APP/PS1 mice.Multivariate statistical analysis was performed to explore the changes in GLS molecular species.Finally,real-time quantitative polymerase chain reaction(RT-qPCR)was employed to determine the mRNA levels of the genes involved in GLS synthesis and catabolism.The results showed that GM1 improved the spatial learning and memory ability,elevated the total GLS level,and modulated the levels of GLS subclasses in the cerebral cortex of APP/PS1 mice.The ingestion of GM1 significantly up-regulated the mRNA levels of the genes(st3gal5p1,st8sia1,b3galt4,st3gal2,and soat)involved in GLS synthesis and down-regulated the mRNA levels of hexa associated with GLS catabolism.In conclusion,dietary GM1 can regulate the metabolism of endogenous GLS in the brain of AD mice.