Targeted metabolomics study of early pathological features in hippocampus of triple transgenic Alzheimer’s disease male mice,Journal of Neuroscience Research

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Targeted metabolomics study of early pathological features in hippocampus of triple transgenic Alzheimer’s disease male mice
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-11-16 , DOI: 10.1002/jnr.24750
Yuxi Zhao ₁ , Haiquan Chen ₁ , Javed Iqbal ₁ , Xukun Liu ₁ , Huajie Zhang _{1,

2} , Shifeng Xiao ₁ , Na Jin ₁ , Fang Yao _{1,

3} , Liming Shen ₁

Affiliation

Alzheimer's disease (AD) is a serious neurodegenerative disease in people of age 65 or above. The detailed etiology and pathogenesis of AD have not been elucidated yet. In this study, the hippocampi of 2‐ and 6‐month‐old triple transgenic Alzheimer's disease male mice and age–sex‐matched wild‐type (WT) mice were analyzed by using targeted metabolomics approach. Compared with WT mice, 24 and 60 metabolites were found with significant differences in 2‐ and 6‐month‐old AD mice. Among these, 14 metabolites were found common while 10 metabolites showed consistent variable trends in both groups. These differential metabolites are found associated with amino acid, lipid, vitamin, nucleotide‐related base, neurotransmitter and energy metabolisms, and oxidative stress. The results suggest that these differential metabolites might play a critical role in AD pathophysiology, and may serve as potential biomarkers for AD. Moreover, the results highlight the involvement of abnormal purine, pyrimidine, arginine, and proline metabolism, along with glycerophospholipid metabolism in early pathology of AD. For the first time, several differential metabolites are found to be associated with AD in this study. Targeted metabolomics can be used for rapid and accurate quantitative analysis of specific target metabolites associated with AD.

中文翻译：

三重转基因阿尔茨海默病雄性小鼠海马早期病理特征的靶向代谢组学研究

阿尔茨海默病 (AD) 是一种严重的神经退行性疾病，发生在 65 岁或以上的人群中。AD的详细病因和发病机制尚未阐明。在这项研究中，使用靶向代谢组学方法分析了 2 个月和 6 个月大的三重转基因阿尔茨海默病雄性小鼠和年龄性别匹配的野生型 (WT) 小鼠的海马体。与 WT 小鼠相比，发现 24 和 60 种代谢物在 2 个月和 6 个月大的 AD 小鼠中存在显着差异。其中，发现有 14 种代谢物是常见的，而 10 种代谢物在两组中显示出一致的可变趋势。发现这些差异代谢物与氨基酸、脂质、维生素、核苷酸相关碱基、神经递质和能量代谢以及氧化应激有关。结果表明，这些差异代谢物可能在 AD 病理生理学中起关键作用，并可能作为 AD 的潜在生物标志物。此外，结果强调了异常嘌呤、嘧啶、精氨酸和脯氨酸代谢以及甘油磷脂代谢在 AD 的早期病理中的参与。本研究首次发现几种差异代谢物与 AD 相关。靶向代谢组学可用于快速准确地定量分析与 AD 相关的特定目标代谢物。在这项研究中发现几种不同的代谢物与 AD 相关。靶向代谢组学可用于快速准确地定量分析与 AD 相关的特定目标代谢物。在这项研究中发现几种不同的代谢物与 AD 相关。靶向代谢组学可用于快速准确地定量分析与 AD 相关的特定目标代谢物。

更新日期：2020-11-16

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