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Publication : Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice.

First Author  Guidetti P Year  2006
Journal  Neurobiol Dis Volume  23
Issue  1 Pages  190-7
PubMed ID  16697652 Mgi Jnum  J:111237
Mgi Id  MGI:3653320 Doi  10.1016/j.nbd.2006.02.011
Citation  Guidetti P, et al. (2006) Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. Neurobiol Dis 23(1):190-7
abstractText  The brain levels of the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, the free radical generator 3-hydroxykynurenine (3-HK), are elevated in early stage Huntington disease (HD). We now examined the status of these metabolites in three mouse models of HD. In R6/2 mice, 3-HK levels were significantly and selectively elevated in the striatum, cortex and cerebellum starting at 4 weeks of age. In contrast, both 3-HK and QUIN levels were increased in the striatum and cortex of the full-length HD models, beginning at 8 months (YAC128) and 15 months (Hdh(Q92) and Hdh(Q111)), respectively. No changes were seen in 13-month-old shortstop mice, which show no signs of motor or cognitive dysfunction or selective neuropathology. These results demonstrate both important parallels and intriguing differences in the progressive neurochemical changes in these HD mouse models and support the hypothesis that QUIN may play a role in the striatal and cortical neurodegeneration of HD.
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