Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST-School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea.
Doping Control Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Neuroscience. 2019 Sep 15;416:74-87. doi: 10.1016/j.neuroscience.2019.07.029. Epub 2019 Jul 31.
Multiple sclerosis (MS) is a demyelination disease that causes gradual damage to neurons. Despite the necessity of appropriate treatments at each disease stage to prevent the worsening of the damage, it is still difficult to cure MS. In this study, metabolomics and lipidomics studies were performed with time-course plasma samples (early, peak, chronic phase for MS) to elucidate the mechanism during MS progression after induction of experimental autoimmune encephalomyelitis (EAE), which is the animal model for multiple sclerosis (MS). Plasma samples were analyzed using ultra-high performance liquid chromatography-orbitrap-mass spectrometry (UHPLC-Orbitrap-MS) and metabolic changes were observed using multivariate analysis. We also measured the activity of NADPH and MMP-9 to evaluate the degree of the inflammation during the disease progression. As a result, 49 metabolites, which had significant differences either at each time point or with time-course changes between control (CTL) and EAE groups, were identified. Among them, glycerophospholipids and fatty acyls were downregulated during disease progression compared with the CTL group. However, glycerolipids, taurine-conjugated bile acids (BAs), and sphingolipids exhibited the reverse pattern. These metabolic changes were accompanied by increases in oxidative stress and immune response upon observing the changes in the activities of NADPH oxidase and MMP-9. In particular, 26 metabolites showed significant differences at specific stages. The metabolite level of the plasma was significantly altered in response to the EAE pathogenesis, and these changes were related to inflammation status at each disease stage. This study can provide crucial information for reducing damage by differentiating treatment strategies according to disease progression.
多发性硬化症 (MS) 是一种脱髓鞘疾病，会导致神经元逐渐受损。尽管在每个疾病阶段都需要进行适当的治疗以防止损伤恶化，但仍难以治愈 MS。在这项研究中，对时间进程血浆样本（MS 的早期、高峰期和慢性期）进行了代谢组学和脂质组学研究，以阐明实验性自身免疫性脑脊髓炎 (EAE) 诱导后 MS 进展期间的机制，EAE 是多发性硬化症 (MS) 的动物模型。使用超高效液相色谱-轨道阱质谱 (UHPLC-Orbitrap-MS) 分析血浆样本，并使用多变量分析观察代谢变化。我们还测量了 NADPH 和 MMP-9 的活性，以评估疾病进展过程中的炎症程度。结果，鉴定出 49 种代谢物，它们在每个时间点或 CTL 和 EAE 组之间的时间进程变化中均有显著差异。其中，与 CTL 组相比，疾病进展过程中甘油磷脂和脂肪酸酰基下调。然而，甘油酯、牛磺酸结合胆汁酸 (BAs) 和鞘脂则呈现相反的模式。在观察 NADPH 氧化酶和 MMP-9 活性的变化时，这些代谢变化伴随着氧化应激和免疫反应的增加。特别是，26 种代谢物在特定阶段表现出显著差异。血浆代谢物水平对 EAE 发病机制有明显改变，这些变化与每个疾病阶段的炎症状态有关。这项研究可以提供重要信息，通过根据疾病进展区分治疗策略来减少损伤。
