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Biomedicines
Volume 11
Issue 3
10.3390/biomedicines11030945
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Article

The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis

by
Helga Polyák
1,2,
Zsolt Galla
3,
Nikolett Nánási
4,
Edina Katalin Cseh
1,
Cecília Rajda
1,
Gábor Veres
5,
Eleonóra Spekker
4,
Ágnes Szabó
1,2,
Péter Klivényi
1,
Masaru Tanaka
4,† and
László Vécsei
1,4,*,†
1
Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
2
Doctoral School of Clinical Medicine, University of Szeged, Korányi fasor 6, H-6720 Szeged, Hungary
3
Department of Pediatrics, Albert Szent-Györgyi Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary
4
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
5
Independent Researcher, H-6726 Szeged, Hungary
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2023, 11(3), 945; https://doi.org/10.3390/biomedicines11030945
Submission received: 17 January 2023 / Revised: 7 March 2023 / Accepted: 16 March 2023 / Published: 20 March 2023
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Translational Laboratory and Experimental Medicine for the Sake of Neurological Diseases and Mental Illnesses)
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Abstract

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.
Keywords: multiple sclerosis; PPMS; SPMS; tryptophan; kynurenine; cuprizone; demyelination; remyelination; animal model; translational multiple sclerosis; PPMS; SPMS; tryptophan; kynurenine; cuprizone; demyelination; remyelination; animal model; translational
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MDPI and ACS Style

Polyák, H.; Galla, Z.; Nánási, N.; Cseh, E.K.; Rajda, C.; Veres, G.; Spekker, E.; Szabó, Á.; Klivényi, P.; Tanaka, M.; et al. The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis. Biomedicines 2023, 11, 945. https://doi.org/10.3390/biomedicines11030945

AMA Style

Polyák H, Galla Z, Nánási N, Cseh EK, Rajda C, Veres G, Spekker E, Szabó Á, Klivényi P, Tanaka M, et al. The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis. Biomedicines. 2023; 11(3):945. https://doi.org/10.3390/biomedicines11030945

Chicago/Turabian Style

Polyák, Helga, Zsolt Galla, Nikolett Nánási, Edina Katalin Cseh, Cecília Rajda, Gábor Veres, Eleonóra Spekker, Ágnes Szabó, Péter Klivényi, Masaru Tanaka, and et al. 2023. "The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis" Biomedicines 11, no. 3: 945. https://doi.org/10.3390/biomedicines11030945

APA Style

Polyák, H., Galla, Z., Nánási, N., Cseh, E. K., Rajda, C., Veres, G., Spekker, E., Szabó, Á., Klivényi, P., Tanaka, M., & Vécsei, L. (2023). The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis. Biomedicines, 11(3), 945. https://doi.org/10.3390/biomedicines11030945

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