Cuprizone markedly decreases kynurenic acid levels in the rodent brain tissue and plasma

Helga Polyák; Edina Katalin Cseh; Zsuzsanna Bohár; Cecilia Rajda; Dénes Zádori; Péter Klivényi; József Toldi; László Vécsei

doi:10.1016/j.heliyon.2021.e06124

Cuprizone markedly decreases kynurenic acid levels in the rodent brain tissue and plasma

Heliyon. 2021 Feb 1;7(2):e06124. doi: 10.1016/j.heliyon.2021.e06124. eCollection 2021 Feb.

Authors

Helga Polyák¹, Edina Katalin Cseh¹, Zsuzsanna Bohár^{1

2}, Cecilia Rajda¹, Dénes Zádori¹, Péter Klivényi¹, József Toldi³, László Vécsei^{1

2}

Affiliations

¹ Department of Neurology, Interdisciplinary Centre of Excellence, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
² MTA-SZTE Neuroscience Research Group, Szeged, Hungary.
³ Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.

Abstract

Background: The kynurenine (KYN) pathway (KP) of the tryptophan (TRP) metabolism seems to play a role in the pathomechanism of multiple sclerosis (MS). Cuprizone (CPZ) treated animals develop both demyelination (DEM) and remyelination (REM) in lack of peripheral immune response, such as the lesion pattern type III and IV in MS, representing primary oligodendrogliopathy.

Objective: To measure the metabolites of the KP in the CPZ treated animals, including TRP, KYN and kynurenic acid (KYNA). We proposed that KYNA levels might be decreased in the CPZ-induced demyelinating phase of the animal model of MS, which model represents the progressive phase of the disease.

Methods: A total of 64 C57Bl/6J animals were used for the study. Immunohistochemical (IHC) measurements were performed to prove the effect of CPZ, whereas high-performance liquid chromatography (HPLC) was used to quantify the metabolites of the KP (n = 10/4 groups; DEM, CO1, REM, CO2).

Results: IHC measurements proved the detrimental effects of CPZ. HPLC measurements demonstrated a decrease of KYNA in the hippocampus (p < 0.05), somatosensory cortex (p < 0.01) and in plasma (p < 0.001).

Conclusion: This is the first evidence of marked reduction in KYNA levels in a non-immune mediated model of MS. Our results suggest an involvement of the KP in the pathomechanism of MS, which needs to be further elucidated.

Keywords: Cuprizone; Demyelination; Kynurenic acid; Kynurenine pathway; Multiple sclerosis; Remyelination.