Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a (13)C NMR metabolomic study.
Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a (13)C NMR metabolomic study.
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10 月龄 APP/PS1 转基因小鼠大脑中葡萄糖的代谢命运：(13)C NMR 代谢组学研究。
DOI：
10.1007/s11011-018-0274-7
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发表时间：
2018
影响因子：
3.6
通讯作者：
Gao Hongchang
中科院分区：
文献类型：
--
作者：
Zhou Qi;Zheng Hong;Chen Jiuxia;Li Chen;Du Yao;Xia Huanhuan;Gao Hongchang
阿尔茨海默病（Alzheimer's disease，AD）与脑葡萄糖代谢紊乱有关。本研究采用13 C NMR代谢组学结合静脉输注[1- 13 C]-葡萄糖研究了10月龄APP/PS1转基因淀粉样蛋白病理小鼠模型的脑葡萄糖代谢。我们发现，相对于野生型（WT）小鼠，APP/PS1小鼠的脑葡萄糖显著积累。在APP/PS1小鼠的脑中，还检测到[1- 13 C]-葡萄糖导致的13 C流入三羧酸（TCA）中间体（琥珀酸）以及神经递质（谷氨酸、谷氨酰胺、γ-氨基丁酸和天冬氨酸）的特定碳位点的减少。此外，我们的研究结果表明，13 C-富集的丙氨酸C3显着降低，乳酸C3有降低的趋势，在APP/PS1小鼠比WT小鼠的脑。总而言之，淀粉样蛋白病理学的发展可能会导致葡萄糖利用的减少，并进一步导致能量和神经递质代谢以及大脑中乳酸-丙氨酸穿梭的减少。
Alzheimer’s disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using13C NMR metabolomics in combination with intravenous [1-13C]-glucose infusion in APP/PS1 transgenic mouse model of amyloid pathology at 10 months of age. We found that brain glucose was significantly accumulated in APP/PS1 mice relative to wild-type (WT) mice. Reductions in13C fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, γ-aminobutyric acid and aspartate) from [1-13C]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the13C-enrichments of the C3 of alanine were significantly lower and the C3 of lactate have a tendency to be lower in the brain of APP/PS1 mice than WT mice. Taken together, the development of amyloid pathology could cause a reduction in glucose utilization and further result in decreases in energy and neurotransmitter metabolism as well as the lactate-alanine shuttle in the brain.