期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 26, 页码 6914-6922出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1569-07.2007
关键词
dopaminergic neurons; iron; paraquat; Parkinsonism; risk factors; sporadic
资金
- NIEHS NIH HHS [U54 ES012077, U54 ES12077] Funding Source: Medline
Extensive epidemiological data in humans and studies in animal models of Parkinson's disease (PD) suggest that sporadic forms of the disorder are not strictly genetic in nature but most likely because of combined environmental exposures over the period of the life-span coupled with increased genetic susceptibilities. Environmental paraquat and neonatal iron exposure have both been separately suggested as potential risk factors for sporadic forms of the disease. In this study, we demonstrate that combined environmental exposure to these two agents results in accelerated age-related degeneration of nigrostriatal dopaminergic neurons. Furthermore, pretreatment with the synthetic superoxide dismutase/catalase mimetic, EUK-189, significantly attenuated neuronal death mediated by combined paraquat and iron treatment. These findings support the notion that environmental PD risk factors may act synergistically to produce neurodegeneration associated with the disorder and that iron and paraquat may act via common oxidative stress-mediated mechanisms.
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