Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer's disease
Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2006.08.002
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发表时间：
2007-12-01
影响因子：
4.2
通讯作者：
Page, Guylene
中科院分区：
文献类型：
--
作者：
Barrier, Laurence;Ingrand, Sabrina;Page, Guylene
在这项研究中，脑神经节苷脂的不同转基因小鼠模型的阿尔茨海默病（AD）进行了分析和比较，与年龄匹配的野生型小鼠。在大脑皮层（具有广泛A β斑块的区域）和小脑（不含A β斑块的非易损区域）中分析神经节苷脂。有一个显着增加，简单的神经节苷脂GM 2和GM 3只在所有表达APP（SL）的小鼠皮层。此外，在APP/PS1 Ki模型中记录了复合“a”神经节苷脂（GT 1a、GD 1a和GM 1）的损失，而在APP（SL）和APP/PS1小鼠中，复合“B”神经节苷脂（GQ 1 B、GT 1 B和GD 1 B）中度减少。令人惊讶的是，单独表达突变体PS1（M146 L）或PS1突变体FAD（Ki模型）倾向于降低皮质内GM 2和GM 3的水平。相反，只有轻微的变化，神经节苷脂模式被发现在小脑。由于APP转基因小鼠中发生的神经节苷脂改变与在人类AD脑中观察到的相似，因此这些转基因模型将成为进一步研究神经节苷脂代谢改变在AD发病机制中的作用的有价值的工具。(C)2006爱思唯尔公司All rights reserved.
In this study, brain gangliosides of different transgenic mouse models of Alzheimer's disease (AD) were analyzed and compared with age-matched wild-type mice. Gangliosides were analyzed in cerebral cortex, a region with extensive A(3 plaques, and cerebellum, a non-vulnerable region with no A beta containing plaques. There was a marked increase in simple gangliosides GM2 and GM3 only within the cortex of all mice expressing APP(SL). Additionally, loss of complex "a" gangliosides (GT1a, GD1a and GM1) was recorded in APP/PS1Ki model, whereas in APP(SL) and APP/PS1 mice, the complex "b" gangliosides (GQ1b, GT1b and GD1b) moderately decreased. Surprisingly, expression of either mutant PS1(M146L) or PS1 mutant FAD (Ki model) alone tended to lower the levels of both GM2 and GM3 within the cortex. Conversely, only slight changes of the ganglioside pattern were found in the cerebellum. Because ganglioside alterations occurring in APP transgenic mice were similar to those observed in human AD brain, these transgenic models would represent valuable tools to further investigate the role of altered ganglioside metabolism in the pathogenesis of AD. (C) 2006 Elsevier Inc. All rights reserved.