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Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing-Remitting Multiple Sclerosis
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab. (Spjuth group)ORCID-id: 0000-0001-9382-3273
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.ORCID-id: 0000-0003-0214-596X
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0002-8083-2864
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.ORCID-id: 0000-0002-7045-1806
Vise andre og tillknytning
2019 (engelsk)Inngår i: Cells, ISSN 2073-4409, Vol. 8, nr 2, artikkel-id 84Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

sted, utgiver, år, opplag, sider
2019. Vol. 8, nr 2, artikkel-id 84
Emneord [en]
cerebrospinal fluid, mass spectrometry, metabolomics, multiple sclerosis, pyrimidine, tryptophan
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-375564DOI: 10.3390/cells8020084ISI: 000460896000006PubMedID: 30678351OAI: oai:DiVA.org:uu-375564DiVA, id: diva2:1284187
Forskningsfinansiär
Åke Wiberg FoundationEU, Horizon 2020, 654241Tilgjengelig fra: 2019-01-31 Laget: 2019-01-31 Sist oppdatert: 2019-04-11bibliografisk kontrollert

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