Age-related alterations in the metabolic profile in the hippocampus of the senescence-accelerated mouse prone 8: a spontaneous Alzheimer's disease mouse model.
Age-related alterations in the metabolic profile in the hippocampus of the senescence-accelerated mouse prone 8: a spontaneous Alzheimer's disease mouse model.
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DOI：
10.3233/jad-131463
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Wang H;Lian K;Han B;Wang Y;Kuo SH;Geng Y;Qiang J;Sun M;Wang M
阿尔茨海默病（AD）是最常见的年龄依赖性神经退行性疾病，其导致认知功能的进行性下降。AD的代谢机制是近年来才出现的。在这项研究中，我们使用气相色谱-质谱测量的多变量分析，以确定学习和保留相关的代谢谱在衰老过程中改变在海马体的衰老加速小鼠倾向8（SAMP 8）。与年轻小鼠相比，在成熟和老年小鼠中检测到17种代谢物的变化（13种代谢物减少，4种代谢物增加），包括与脂质代谢功能障碍相关的代谢物（胆固醇、油酸和磷酸甘油酯水平显著升高），氨基酸减少（丙氨酸、丝氨酸、甘氨酸、天冬氨酸、谷氨酸和γ-氨基丁酸）和能量相关代谢物水平（苹果酸，丁二酸，富马酸和柠檬酸），和其他改变代谢物（增加N-乙酰天冬氨酸和减少焦谷氨酸，尿素和乳酸）在海马。所有这些变化表明，SAMP 8小鼠年龄相关性认知障碍的代谢机制与多种途径和网络有关。脂质代谢，尤其是胆固醇代谢，似乎在AD的海马中起着独特的作用。
Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD.