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

Helga Polyák1,2, Zsolt Galla3, Nikolett Nánási4

  • 1Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.

Biomedicines
|March 29, 2023
PubMed

Insights

This study reveals that specific kynurenine (KYN) metabolites are reduced in the cuprizone-induced demyelination mouse model, offering potential biomarkers for progressive multiple sclerosis (MS) and personalized treatment strategies.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Immunology

Background:

  • Progressive multiple sclerosis (MS) is a chronic neurological disease characterized by specific lesion patterns.
  • Aberrations in the tryptophan (TRP)-kynurenine (KYN) metabolic pathway are implicated in MS, but the metabolite profile in progressive MS is not fully understood.
  • The cuprizone (CPZ) toxin-induced mouse model mimics aspects of MS demyelination.

Purpose of the Study:

  • To investigate the kynurenine (KYN) metabolite profile in a cuprizone (CPZ)-induced mouse model of demyelination.
  • To identify potential biomarkers for progressive multiple sclerosis (MS) within the KYN pathway.
  • To explore new avenues for personalized treatment strategies in MS.

Main Methods:

  • C57Bl/6J male mice were treated with 0.2% CPZ for 5 weeks, followed by 4 weeks of recovery.
  • Body weight and immunohistochemistry were used to confirm demyelination.
  • Ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was employed to measure serotonin, TRP, and KYN metabolites in plasma and brain samples at various time points during demyelination and remyelination.

Main Results:

  • A significant reduction in kynurenic acid, 3-hydroxykynurenine (3-HK), and xanthurenic acid was observed in plasma at week 5 of demyelination.
  • Significant reductions in 3-HK and anthranilic acid were found in brain samples at week 5.
  • These findings establish the KYN metabolite profile in the CPZ-induced demyelination model.

Conclusions:

  • The kynurenine (KYN) metabolite profile in the CPZ-induced demyelination model provides insights into metabolic changes during MS.
  • Altered KYN metabolite levels may serve as potential biomarkers for progressive multiple sclerosis (MS).
  • Identifying these biomarkers could facilitate the development of personalized treatment approaches for MS, moving beyond solely immunological considerations.
Keywords:
PPMSSPMSanimal modelcuprizonedemyelinationkynureninemultiple sclerosisremyelinationtranslationaltryptophan

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