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Metabolomic study of disease progression in scrapie prion infected mice; validation of a novel method for brain metabolite extraction.
Metabolomics ( IF 3.6 ) Pub Date : 2020-06-12 , DOI: 10.1007/s11306-020-01690-2
Ze-Lin Fu 1, 2 , Pascal Mercier 3 , Ghazaleh Eskandari-Sedighi 1, 2 , Jing Yang 2 , David Westaway 1, 2 , Brian D Sykes 1
Affiliation  

Introduction

Prion disease is a form of neurodegenerative disease caused by the misfolding and aggregation of cellular prion protein (PrPC). The neurotoxicity of the misfolded form of prion protein, PrPSc still remains understudied. Here we try to investigate this issue using a metabolomics approach.

Objectives

The intention was to identify and quantify the small-in-size and water-soluble metabolites extracted from mice brains infected with the Rocky Mountain Laboratory isolate of mouse-adapted scrapie prions (RML) and track changes in these metabolites during disease evolution.

Methods

A total of 73 mice were inoculated with RML prions or normal brain homogenate control; brains were harvested at 30, 60, 90, 120 and 150 days post-inoculation (dpi). We devised a high-efficiency metabolite extraction method and used nuclear magnetic resonance spectroscopy to identify and quantify 50 metabolites in the brain extracts. Data were analyzed using multivariate approach.

Results

Brain metabolome profiles of RML infected animals displayed continuous changes throughout the course of disease. Among the analyzed metabolites, the most noteworthy changes included increases in myo-inositol and glutamine as well as decreases in 4-aminobutyrate, acetate, aspartate and taurine.

Conclusion

We report a novel metabolite extraction method for lipid-rich tissue. As all the major metabolites are identifiable and quantifiable by magnetic resonance spectroscopy, this study suggests that tracking of neurochemical profiles could be effective in monitoring the progression of neurodegenerative diseases and useful for assessing the efficacy of candidate therapeutics.



中文翻译:

痒病病毒感染小鼠疾病进展的代谢组学研究;新型脑代谢物提取方法的验证。

介绍

on病毒疾病是由细胞pr病毒蛋白(PrP C)的错误折叠和聚集引起的一种神经退行性疾病。错折叠形式的Pr病毒蛋白PrP Sc的神经毒性仍未得到充分研究。在这里,我们尝试使用代谢组学方法研究此问题。

目标

目的是鉴定和量化从被落基山实验室分离的小鼠适应性瘙痒病ions病毒(RML)感染的小鼠大脑中提取的小尺寸和水溶性代谢物,并跟踪疾病发展过程中这些代谢物的变化。

方法

总共73只小鼠接种了RML pr病毒或正常的脑匀浆对照。在接种后30、60、90、120和150天(dpi)收获大脑。我们设计了一种高效的代谢物提取方法,并使用核磁共振波谱法鉴定和定量了脑提取物中的50种代谢物。使用多元方法分析数据。

结果

RML感染动物的脑代谢组谱在整个疾病过程中显示出连续变化。在分析的代谢产物中,最值得注意的变化包括肌醇和谷氨酰胺的增加,以及4-氨基丁酸酯,乙酸盐,天冬氨酸和牛磺酸的减少。

结论

我们报告了富含脂质的组织的新型代谢物提取方法。由于所有主要代谢物都可以通过磁共振波谱进行识别和量化,因此这项研究表明,跟踪神经化学特征可以有效地监测神经退行性疾病的进展,并有助于评估候选疗法的疗效。

更新日期:2020-06-12
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