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

Gábor Veres, Máté Molnár, Dénes Zádori, Márton Szentirmai, Levente Szalárdy, Rita Török, Emese Fazekas, I. Ilisz, L. Vécsei, P. Klivényi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalPharmacology, Biochemistry and Behavior
Volume132
DOIs
Publication statusPublished - 2015

Fingerprint

Huntington Disease
Neurology
Kynurenine
Metabolism
Tryptophan
Central Nervous System
Metabolites
Cerebellum
Rotarod Performance Test
Kynurenic Acid
Aptitude
Genetic Models
Brain Stem
Hippocampus
Brain
Animals
Animal Models
Costs and Cost Analysis
Injections
3-nitropropionic acid

Keywords

  • 3-Nitropropionic acid
  • Behavioral alterations
  • HPLC
  • Huntington's disease
  • Tryptophan metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

Central nervous system-specific alterations in the tryptophan metabolism in the 3-nitropropionic acid model of Huntington's disease. / Veres, Gábor; Molnár, Máté; Zádori, Dénes; Szentirmai, Márton; Szalárdy, Levente; Török, Rita; Fazekas, Emese; Ilisz, I.; Vécsei, L.; Klivényi, P.

In: Pharmacology, Biochemistry and Behavior, Vol. 132, 2015, p. 115-124.

Research output: Contribution to journalArticle

Veres, Gábor ; Molnár, Máté ; Zádori, Dénes ; Szentirmai, Márton ; Szalárdy, Levente ; Török, Rita ; Fazekas, Emese ; Ilisz, I. ; Vécsei, L. ; Klivényi, P. / Central nervous system-specific alterations in the tryptophan metabolism in the 3-nitropropionic acid model of Huntington's disease. In: Pharmacology, Biochemistry and Behavior. 2015 ; Vol. 132. pp. 115-124.
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AU - Veres, Gábor

AU - Molnár, Máté

AU - Zádori, Dénes

AU - Szentirmai, Márton

AU - Szalárdy, Levente

AU - Török, Rita

AU - Fazekas, Emese

AU - Ilisz, I.

AU - Vécsei, L.

AU - Klivényi, P.

PY - 2015

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AB - 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.

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