Identification of Altered Metabolic Pathways during Disease Progression in EAE Mice via Metabolomics and Lipidomics

Title
Identification of Altered Metabolic Pathways during Disease Progression in EAE Mice via Metabolomics and Lipidomics
Authors
권오승정병화이가경Mahbub Hasan
Keywords
EAE; multiple sclerosis; metabolomics; lipidomics; neuroinflammation
Issue Date
2019-09
Publisher
Neuroscience
Citation
VOL 416-87
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/69763
ISSN
0306-4522
Appears in Collections:
KIST Publication > Article
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