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Our objective in this study was to delineate age\u2010related KP alterations in this model. Three enzymes potentially catalyze the first step of the KP; <jats:italic>Ido1<\/jats:italic> and Indoleamine 2,3 dioxygenase\u20102 were highly expressed in the striatum and Tryptophan 2,3 dioxygenase (<jats:italic>Tdo2<\/jats:italic>) in the cerebellum. During development, <jats:italic>Ido1<\/jats:italic> mRNA expression is dynamically regulated and chronically up\u2010regulated in YAC128 mice. Kynurenine (Kyn) to tryptophan (Trp) ratio, a measure of activity in the first step of the KP, was elevated in YAC128 striatum, but no change in <jats:italic>Tdo2<\/jats:italic> mRNA levels or Kyn to Trp ratio was detected in the cerebellum. Ido1 induction was coincident with Trp depletion at 3\u00a0months and Kyn accumulation at 12\u00a0months of age in striatum. Changes in downstream KP metabolites of YAC128 mice generally followed a biphasic pattern with neurotoxic metabolites reduced at 3\u00a0months and increased at 12\u00a0months of age. Striatally specific induction of <jats:italic>Ido1<\/jats:italic> and downstream KP alterations suggest involvement in HD pathogenesis, and should be taken into account in future therapeutic developments for HD.<\/jats:p>","DOI":"10.1111\/jnc.12350","type":"journal-article","created":{"date-parts":[[2013,6,21]],"date-time":"2013-06-21T09:07:51Z","timestamp":1371805671000},"page":"852-867","source":"Crossref","is-referenced-by-count":31,"title":["Age\u2010dependent alterations of the kynurenine pathway in the <scp>YAC<\/scp>128 mouse model of Huntington disease"],"prefix":"10.1111","volume":"127","author":[{"given":"Gelareh","family":"Mazarei","sequence":"first","affiliation":[{"name":"Centre for Molecular Medicine &amp; Therapeutics and Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Budac","sequence":"additional","affiliation":[{"name":"Lundbeck Research USA Paramus New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Lu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine &amp; Therapeutics and Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Adomat","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma S.","family":"Tomlinson Guns","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Lundbeck Research USA Paramus New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R.","family":"Leavitt","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine &amp; Therapeutics and Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada"},{"name":"Division of Neurology Department of Medicine University of British Columbia Hospital Vancouver British Columbia Canada"},{"name":"Brain Research Centre University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. 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