Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease,FEBS Open Bio

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Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
FEBS Open Bio ( IF 2.8 ) Pub Date : 2021-09-01 , DOI: 10.1002/2211-5463.13285
Masayo Hashimoto ₁ , Kenichi Watanabe ₁ , Kan Miyoshi ₂ , Yukako Koyanagi ₂ , Jun Tadano ₁ , Izuru Miyawaki ₁

Affiliation

Huntington’s disease (HD) is a progressive, neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. To investigate the metabolic alterations that occur in HD, here we examined plasma and whole-brain metabolomic profiles of the R6/2 mouse model of HD. Plasma and brain metabolomic analyses were conducted using capillary electrophoresis–mass spectrometry (CE-MS). In addition, liquid chromatography–mass spectrometry (LC-MS) was also applied to plasma metabolomic analyses, to cover the broad range of metabolites with various physical and chemical properties. Various metabolic alterations were identified in R6/2 mice. We report for the first time the perturbation of histidine metabolism in the brain of R6/2 mice, which was signaled by decreases in neuroprotective dipeptides and histamine metabolites, indicative of neurodegeneration and an altered histaminergic system. Other differential metabolites were related to arginine metabolism and cysteine and methionine metabolism, suggesting upregulation of the urea cycle, perturbation of energy homeostasis, and an increase in oxidative stress. In addition, remarkable changes in specific lipid classes are indicative of dysregulation of lipid metabolism. These findings provide a deeper insight into the metabolic alterations that occur in HD and provide a foundation for the future development of HD therapeutics.

中文翻译：

亨廷顿病 R6/2 小鼠模型的多平台代谢组学分析

亨廷顿病 (HD) 是一种进行性神经退行性疾病，其特征是运动、认知和精神症状。为了研究 HD 中发生的代谢变化，我们检查了 HD 的 R6/2 小鼠模型的血浆和全脑代谢组谱。使用毛细管电泳质谱（CE-MS）进行血浆和脑代谢组学分析。此外，液相色谱-质谱（LC-MS）也应用于血浆代谢组学分析，以涵盖具有各种物理和化学性质的广泛代谢物。在 R6/2 小鼠中发现了各种代谢改变。我们首次报告了 R6/2 小鼠大脑中组氨酸代谢的扰动，其信号是神经保护性二肽和组胺代谢物的减少，表明神经退行性变和组胺能系统的改变。其他差异代谢物与精氨酸代谢以及半胱氨酸和蛋氨酸代谢相关，表明尿素循环上调、能量稳态扰乱以及氧化应激增加。此外，特定脂质类别的显着变化表明脂质代谢失调。这些发现提供了对HD中发生的代谢改变的更深入的了解，并为HD疗法的未来发展奠定了基础。

更新日期：2021-10-02

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