Central nervous system-specific alterations in the tryptophan metabolism in the 3-nitropropionic acid model of Huntington's disease

• 3-Nitropropionic acid was used to model Huntington's disease in C57Bl/6 mice.
• The alterations in the tryptophan metabolism were examined.
• Behavior was assessed through open-field, rotarod and Y-maze tests.
• An increased kynurenine/tryptophan ratio was found in several brain regions.
• The results of behavioral assessments were similar to previously published ones.

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.