期刊
JOURNAL OF NEURAL TRANSMISSION
卷 116, 期 9, 页码 1079-1086出版社
SPRINGER WIEN
DOI: 10.1007/s00702-009-0253-6
关键词
Huntington's disease; Probenecid; Kynurenic acid; Neuroprotection
资金
- RET-NORT [08/2004]
- ETT [275/2006]
Huntington's disease (HD) is an autosomal dominantly inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage and altered membrane transport may have an important role in the pathogenesis of HD. Probenecid is a non-selective inhibitor of multidrug resistance-associated proteins, but it also inhibits organic anion transporters. In this study, we examined the effects of probenecid on the survival, behaviour and immunohistochemical changes in the N171-82Q transgenic mouse model of HD. After probenecid administration, the duration of survival improved by 35%. The motor activity was significantly ameliorated as compared with the control transgenic group. Probenecid treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates. These results suggest that probenecid may exert a neuroprotective effect by increasing the membrane transport of protective compounds, and/or inhibiting the toxic compounds.
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