The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis
Helga Polyák,
Zsolt Galla,
Nikolett Nánási,
Edina Katalin Cseh,
Cecília Rajda,
Gábor Veres,
Eleonóra Spekker,
Ágnes Szabó,
Péter Klivényi,
Masaru Tanaka,
László Vécsei
Affiliations
Helga Polyák
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Zsolt Galla
Department of Pediatrics, Albert Szent-Györgyi Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary
Nikolett Nánási
Danube Neuroscience Research Laboratory, ELKH-SZTE Neuroscience Research Group, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
Edina Katalin Cseh
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Cecília Rajda
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Gábor Veres
Independent Researcher, H-6726 Szeged, Hungary
Eleonóra Spekker
Danube Neuroscience Research Laboratory, ELKH-SZTE Neuroscience Research Group, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
Ágnes Szabó
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Péter Klivényi
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Masaru Tanaka
Danube Neuroscience Research Laboratory, ELKH-SZTE Neuroscience Research Group, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
László Vécsei
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Progressive multiple sclerosis (MS) is a chronic disease with a unique pattern, which is histologically classified into the subpial type 3 lesions in the autopsy. The lesion is also homologous to that of cuprizone (CPZ) toxin-induced animal models of demyelination. Aberration of the tryptophan (TRP)-kynurenine (KYN) metabolic system has been observed in patients with MS; nevertheless, the KYN metabolite profile of progressive MS remains inconclusive. In this study, C57Bl/6J male mice were treated with 0.2% CPZ toxin for 5 weeks and then underwent 4 weeks of recovery. We measured the levels of serotonin, TRP, and KYN metabolites in the plasma and the brain samples of mice at weeks 1, 3, and 5 of demyelination, and at weeks 7 and 9 of remyelination periods by ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) after body weight measurement and immunohistochemical analysis to confirm the development of demyelination. The UHPLC-MS/MS measurements demonstrated a significant reduction of kynurenic acid, 3-hydoxykynurenine (3-HK), and xanthurenic acid in the plasma and a significant reduction of 3-HK, and anthranilic acid in the brain samples at week 5. Here, we show the profile of KYN metabolites in the CPZ-induced mouse model of demyelination. Thus, the KYN metabolite profile potentially serves as a biomarker of progressive MS and thus opens a new path toward planning personalized treatment, which is frequently obscured with immunologic components in MS deterioration.
