Iron and Paraquat are Synergistic Risk Factors for Parkinson’s Disease

Julie K. Andersen, Ph.D.
Buck Institute for Age Research
U54012077

In recent research by NIEHS grantee Julie Andersen of the Buck Institute for Age Research in Novato, Ca, mice exposed to iron and the pesticide paraquat show accelerated age-related damage in neurons associated with Parkinson’s disease. In addition, mice pretreated with an antioxidant had a less severe affect suggesting iron and paraquat damage the neurons through oxidative stress mechanisms.

Previous research sponsored in part by NIEHS highlighted the role environmental factors play in the development of Parkinson’s disease. Only five percent of the 160,000 Parkinson’s cases diagnosed each year in the U.S. are strictly the result of genetics. The vast majority of cases are thought to be the result of environmental exposures and genetic susceptibilities.

Both high doses of iron given at infancy and paraquat have been shown to cause Parkinson-like symptoms in mice. In the current study, genetically identical mice were divided into four groups. One group was given excess iron during infancy; one group was given paraquat; a third group was given both agents; and the fourth group did not receive either agent. Half the animals in each group were given an antioxidant. Results show that exposing the mice to both agents accelerated the Parkinson-like neurodegeneration with the symptoms starting at the human equivalent of middle-age. The mice exhibited increased oxidative stress followed by decreased neuronal function and finally neuronal cell death. The mice co-treated with the antioxidant showed significantly less nerve cell death in the area of the brain associated with Parkinson’s disease.

This study points to the need for an early diagnostic test for Parkinson’s disease to identify people in need of antioxidant interventions prior to the development of symptoms. It also shows that seemingly harmless early life exposures can work in concert with subsequent exposures to exacerbate neurodegeneration.

Citation: Peng J, Peng L, Stevenson FF, Doctrow SR, Andersen JK. Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson's disease accelerate age-related neurodegeneration. J Neurosci. 2007 Jun 27;27(26):6914-22.