title: Central nervous system-specific alterations in the tryptophan metabolism in the 3-nitropropionic acid model of Huntington's disease.
abstract: Experiments on human samples and on genetic animal models of Huntington's disease (HD) suggest that a number of neuroactive metabolites in the kynurenine (KYN) pathway (KP) of the tryptophan (TRP) catabolism may play a role in the development of HD. Our goal in this study was to assess the concentrations of TRP, KYN, kynurenic acid and 3-hydroxykynurenine (3-OHK) in the serum and brain of 5-month-old C57Bl/6 mice in the widely used 3-nitropropionic acid (3-NP) toxin model of HD. We additionally investigated the behavioral changes through open-field, rotarod and Y-maze tests. Our findings revealed an increased TRP catabolism via the KP as reflected by elevated KYN/TRP ratios in the striatum, hippocampus, cerebellum and brainstem. As regards the other examined metabolites of KP, we found only a significant decrease in the 3-OHK level in the cerebellum of the 3-NP-treated mice. The open-field and rotarod tests demonstrated that treatment with 3-NP resulted in a reduced motor ability, though this had almost totally disappeared a week after the last injection, similarly as observed previously in most murine 3-NP studies. The relevance of the alterations observed in our biochemical and behavioral analyses is discussed. We propose that the identified biochemical alterations could serve as applicable therapeutic endpoints in studies of drug effects on delayed-type neurodegeneration in a relatively fast and cost-effective toxin model of HD.
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Máté
authors.initials: M
authors.lastname: Molnár
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Zádori
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Szentirmai
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Szalárdy
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Török
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Fazekas
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Ilisz
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary; MTA-SZTE Neuroscience Research Group, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary. Electronic address: klivenyi.peter@med.u-szeged.hu.
authors.forename: Péter
authors.initials: P
authors.lastname: Klivényi
keywords: 3-Nitropropionic acid; Behavioral alterations; HPLC; Huntington's disease; Tryptophan metabolism