title: Ascorbate treatment attenuates the Huntington behavioral phenotype in mice.
abstract: The R6/2 mouse line expresses exon 1 of the human gene for Huntington disease (HD) and shows behavioral symptoms as early as 6 weeks of age. In the striatum, a forebrain target of HD, these animals show a behavior-related deficit in extracellular ascorbate, the deprotonated form of vitamin C. We report here that this deficit may contribute to the HD behavioral phenotype. Regular injections of ascorbate (300 mg/kg/day, 4 days/week) beginning at symptom onset restored the behavior-related release of ascorbate in striatum and also improved behavioral responding. Compared to vehicle, ascorbate treatment significantly attenuated the neurological motor signs of HD without altering overall motor activity. Ascorbate regulation of striatal function appears key for understanding HD.
authors.affiliation: Department of Psychology, Indiana University, Bloomington, IN 47405, USA. REBEC@indiana.edu
authors.forename: George V
authors.initials: GV
authors.lastname: Rebec
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Barton
authors.forename: Ann M
authors.initials: AM
authors.lastname: Marseilles
authors.forename: Kristin
authors.initials: K
authors.lastname: Collins
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype
chemical_list: C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D001205:Ascorbic Acid