Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease.
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.
Bogdanov
M B
MB
Neurochemistry Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Ferrante
R J
RJ
Kuemmerle
S
S
Klivenyi
P
P
Beal
M F
MF
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
D062385:Hydroxybenzoates; D009574:Nitro Compounds; D010226:Parabens; D011422:Propionates; D017665:Hydroxyl Radical; C009091:protocatechuic acid; C038193:4-hydroxybenzoic acid; C015392:3-nitropropionic acid