Alterations in neuronal metabolism contribute to the pathogenesis of prion disease
Alterations in neuronal metabolism contribute to the pathogenesis of prion disease
复制标题
DOI：
10.1038/s41418-018-0148-x
复制
发表时间：
2018-08-01
影响因子：
12.4
通讯作者：
Steinert, Joern R.
中科院分区：
文献类型：
--
作者：
Bourgognon, Julie-Myrtille;Spiers, Jereme G.;Steinert, Joern R.
神经退行性疾病的特征是神经元逐渐丧失，这被认为是由错误折叠的蛋白质聚集引起的。在此期间，许多生理和代谢组学的改变以及基因表达的变化导致神经元功能下降。然而，这些病理效应尚未得到充分表征。在这项研究中，我们利用代谢组学方法来研究感染错误折叠朊病毒蛋白的小鼠海马体和皮质中发生的代谢变化。为了识别这些变化，通过超高效液相色谱-串联质谱法对样品进行了分析。目前的数据集总共包含 498 种已知身份的化合物，称为生化物质，它们已经过主成分分析和监督机器学习。产生的结果与接种朊病毒的小鼠代谢谱显着改变一致。我们特别强调与葡萄糖、神经肽、脂肪酸、L-精氨酸/一氧化氮和前列腺素代谢相关的变化，所有这些在疾病期间都会发生显着变化。这些数据为未来针对特定途径的研究提供了可能性，以更好地了解神经退行性疾病中神经元功能障碍所涉及的过程。
Neurodegenerative conditions are characterised by a progressive loss of neurons, which is believed to be initiated by misfolded protein aggregations. During this time period, many physiological and metabolomic alterations and changes in gene expression contribute to the decline in neuronal function. However, these pathological effects have not been fully characterised. In this study, we utilised a metabolomic approach to investigate the metabolic changes occurring in the hippocampus and cortex of mice infected with misfolded prion protein. In order to identify these changes, the samples were analysed by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. The present dataset comprises a total of 498 compounds of known identity, named biochemicals, which have undergone principal component analysis and supervised machine learning. The results generated are consistent with the prion-inoculated mice having significantly altered metabolic profiles. In particular, we highlight the alterations associated with the metabolism of glucose, neuropeptides, fatty acids, L-arginine/nitric oxide and prostaglandins, all of which undergo significant changes during the disease. These data provide possibilities for future studies targeting and investigating specific pathways to better understand the processes involved in neuronal dysfunction in neurodegenerative diseases.