Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington's disease.

ABSTRACT: Elevated concentrations of neurotoxic metabolites of the kynurenine pathway (KP) of tryptophan degradation may play a causative role in Huntington's disease (HD). The brain levels of one of these compounds, 3-hydroxykynurenine (3-HK), are increased in both HD and several mouse models of the disease. In the present study, we examined this impairment in greater detail using the R6/2 mouse, a well-established animal model of HD. Initially, mutant and age-matched wild-type mice received an intrastriatal injection of (3)H-tryptophan to assess the acute, local de novo production of kynurenine, the immediate bioprecursor of 3-HK, in vivo. No effect of genotype was observed between 4 and 12 weeks of age. In contrast, intrastriatally applied (3)H-kynurenine resulted in significantly increased neosy

SUBMITTER: Sathyasaikumar KV 

PROVIDER: S-EPMC3721540 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature