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Cells 2019, 8(2), 84; https://doi.org/10.3390/cells8020084

Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis

1
Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden
2
Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, 751 24 Uppsala, Sweden
3
Department of Neuroscience, Uppsala University, 751 85 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Received: 14 December 2018 / Revised: 16 January 2019 / Accepted: 22 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue The Molecular and Cellular Basis for Multiple Sclerosis)
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Abstract

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. View Full-Text
Keywords: multiple sclerosis; cerebrospinal fluid; metabolomics; mass spectrometry; tryptophan; pyrimidine multiple sclerosis; cerebrospinal fluid; metabolomics; mass spectrometry; tryptophan; pyrimidine
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Herman, S.; Åkerfeldt, T.; Spjuth, O.; Burman, J.; Kultima, K. Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis. Cells 2019, 8, 84.

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