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

Pharmacology, Biochemistry, and Behavior
Gábor VeresPeter Klivenyi

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 tha...Continue Reading

References

Sep 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·T A AlstonH J Bright
Mar 1, 1992·Journal of the Neurological Sciences·M F BealE D Bird
Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R SchwarczW O Whetsell
Sep 1, 1974·Neurology·W L Stahl, P D Swanson
Jan 1, 1995·Brain Research Bulletin·C V BorlonganP R Sanberg
Aug 1, 1997·The American Journal of Psychiatry·M DiFiglia
Sep 13, 2001·Mental Retardation and Developmental Disabilities Research Reviews·M A Nance, R H Myers
Jul 9, 2002·The European Journal of Neuroscience·Pierre-O FernagutFrançois Tison
Oct 31, 2002·Nature Reviews. Drug Discovery·Trevor W Stone, L Gail Darlington
Jun 19, 2003·Human Molecular Genetics·Elizabeth J SlowMichael R Hayden
Dec 2, 2004·Neurobiology of Disease·Paolo GuidettiRobert Schwarcz
Nov 22, 2005·Neurobiology of Disease·Peter KlivenyiM Flint Beal
May 16, 2006·Neurobiology of Disease·Paolo GuidettiRobert Schwarcz
Aug 23, 2007·ILAR Journal·Shilpa RamaswamyJeffrey H Kordower
Dec 17, 2008·Annals of the New York Academy of Sciences·Susan E Browne
Jun 6, 2009·Cellular and Molecular Neurobiology·Yuen-Shan HoRaymond Chuen-Chung Chang
Mar 20, 2010·Journal of Neurochemistry·Korrapati V SathyasaikumarRobert Schwarcz
Mar 26, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isaac TúnezAbel Santamaría
Dec 16, 2010·Journal of Cellular and Molecular Medicine·Dénes ZádoriLászló Vécsei

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Citations

Dec 13, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lu WangQi Yang
Nov 20, 2018·Expert Opinion on Therapeutic Targets·Fanni A BorosLászló Vécsei
Jun 30, 2019·Frontiers in Cellular and Infection Microbiology·Dezső P VirokKatalin Burián
Mar 9, 2021·Frontiers in Cellular Neuroscience·Ning DengWei Xie

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