Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice

• Published in: Behavioural brain research 2012-11, Vol.235 (1), p.1-6
• Main Authors: Chen, Shuang-qing, Cai, Qing, Shen, Yu-ying, Wang, Pei-jun, Teng, Gao-jun, Zhang, Wei, Zang, Feng-chao
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Aging - psychology; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - psychology; Alzheimer's disease (AD); Amyloid beta-Protein Precursor - genetics; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biomarkers - metabolism; Choline - metabolism; Creatine - metabolism; Disease Models, Animal; Functional Neuroimaging - methods; Functional Neuroimaging - psychology; Glutamic Acid - metabolism; Hippocampus - metabolism; Inositol - metabolism; Magnetic resonance spectroscopy (MRS); Magnetic Resonance Spectroscopy - methods; Maze Learning - physiology; Metabolite; Mice; Mice, Transgenic; Morris water maze (MWM); Presenilin-1 - genetics; Protons
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.07.016

► 1H-MRS and behavioral testing were performed in different age of APP/PS1 mice. ► The mI levels were significantly higher from 3 months of age in APP/PS1 mice. ► The NAA and Glu level were significantly decreased at 5–8 months of age in APP/PS1 mice. ► Changes in spatial learning and memory only occurred at 8-month-old APP/PS1 mice. ► Metabolic changes in brain preceded overt cognitive dysfunctions in early AD. Proton magnetic resonance spectroscopy (1H-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 1H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. 1H-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 (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The 1H-MRS revealed that mI 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