02704nab a2200337 i 4500 publ26787 20230322133513.0 230322s2023 hu o 0|| Angol d 2227-9059 10.3390/biomedicines11030945 doi 33709302 mtmt SZTE Publicatio Repozitórium hun Angol Polyák Helga The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis [elektronikus dokumentum] / Polyák Helga 2023 20 BIOMEDICINES 11 No. 3 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. Klinikai orvostan Galla Zsolt aut Nánási Nikolett aut Cseh Edina Katalin aut Rajda Cecília aut Veres Gábor aut Spekker Eleonóra aut Szabó Ágnes aut Klivényi Péter aut Tanaka Masaru aut Vécsei László aut http://publicatio.bibl.u-szeged.hu/26787/1/PolyakH._thetryptophan-kynureninemetabolicsystem....pdf Dokumentum-elérés