title: Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease.
abstract: There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease (HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD.
authors.affiliation: Neurochemistry Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Bogdanov
authors.forename: R J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: S
authors.initials: S
authors.lastname: Kuemmerle
authors.forename: P
authors.initials: P
authors.lastname: Klivenyi
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004351:Drug Resistance / Q000502:physiology; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D017551:Microdialysis; D009574:Nitro Compounds; D010226:Parabens / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D012016:Reference Values
chemical_list: D062385:Hydroxybenzoates; D009574:Nitro Compounds; D010226:Parabens; D011422:Propionates; D017665:Hydroxyl Radical; C009091:protocatechuic acid; C038193:4-hydroxybenzoic acid; C015392:3-nitropropionic acid