Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice
Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice
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APP/PS1转基因小鼠大脑代谢物和认知功能与年龄相关的变化
DOI：
10.1016/j.bbr.2012.07.016
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发表时间：
2012-11-01
影响因子：
2.7
通讯作者：
Zang, Feng-chao
中科院分区：
文献类型：
--
作者：
Chen, Shuang-qing;Cai, Qing;Zang, Feng-chao
质子磁共振波谱（H-1-MRS）和Morris水迷宫（MWM）在阿尔茨海默病（AD）研究中发挥了重要作用。本研究的目的是确定H-1-MRS和MWM是否能检测APP/PS1转基因（tg）小鼠的早期AD。20只tg小鼠和15只野生型小鼠在3、5、8月龄时进行H-1-MRS。测定海马组织中n -乙酰天冬氨酸（NAA）、谷氨酸（Glu）、肌醇（ml）、胆碱（Cho）、肌酸（Cr）的浓度，测定NAA/Cr。测定Glu/Cr、ml/Cr、Cho/Cr比值。此外，用MWM评价小鼠的空间学习和记忆能力。H-1-MRS结果显示，tg小鼠3月龄时ml水平显著高于wt小鼠，5、8月龄时NAA、Glu水平显著低于wt小鼠（p < 0.05）。此外，APP/PS1 tg小鼠仅在8月龄时发生显著的认知变化。这些结果表明，代谢变化先于早期AD的明显认知功能障碍，表明H-1-MRS是评估早期AD的更敏感的生物标志物。(c) 2012 Elsevier B.V.版权所有
Proton magnetic resonance spectroscopy (H-1-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether H-1-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. H-1-MRS was performed in 20 tg mice and 15 wild-type mice at 3,5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (ml), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr. Glu/Cr, ml/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The H-1-MRS revealed that ml levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p < 0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that H-1-MRS is a more sensitive biomarker for assessing early AD. (c) 2012 Elsevier B.V. All rights reserved.