The study, published Wednesday in the journal Cell, also identified the mechanism by which the chemicals induce Parkinson’s in those with the mutation. Stuart Lipton of the Sanford-Burnham Medical Research Institute was the study’s senior author. Scott D. Ryan, also of the institute, was first author. Pesticide exposure has long been known as an increased risk factor for Parkinson’s, which gradually reduces the ability to move. However, the reasons for this vulnerability are unknown. The study found one genetic cause; others may also be involved. Environmental factors help determine whether Parkinson's actually develops, the scientists say.
The researchers studied cells from Parkinson’s patients with a mutation suspected of playing a role in the vulnerability. The mutation cause a protein to forms abnormal clumps and filaments in brain cells damaged by Parkinson’s. The clumps, called Lewy bodies, are associated with damage to neurons that make dopamine, a neurotransmitter essential for normal movement. Filaments called Levy neurites also indicate Parkinson's.
photoLevy neurites, filaments indicating Parkinson's disease. These were produced from the skin cells of Parkinson's patients turned into neurons and exposed to pesticides. — Sanford-Burnham Medical Research Institute. Researchers took skin cells from the patients and turned them into artificial embryonic stem cells, called induced pluripotent stem cells, also being researched as a therapy for Parkinson's. Some of the cells from each patient were genetically engineered to correct the defect, the rest were left unaltered. This created two sets of cells, identical except for the mutation.
Then both sets of cells, one with the mutation and one with it corrected, were turned into the dopamine-producing neurons. These neurons were dosed with the pesticides and herbicides. They were the widely used herbicide paraquat, along with the pesticides maneb and rotenone. Paraquat was used in Mexico and the United States to destroy marijuana crops during the 1970s and 1980s in U.S. government-sponsored programs.
The neurons with the uncorrected mutation were more likely to develop damage characteristic of Parkinson’s, even at much lower doses than those allowed by the EPA. Those with corrected mutation were more resistant.
To further test their hypothesis, researchers did a similar experiment with human embryonic stem cells that did not carry the mutation. Some of these cells were genetically engineered to give them the mutation. Both sets were then converted into dopamine-producing neurons. As with the patient-derived cells, those cells carrying the mutation also displayed the increased vulnerability to pesticide exposure.
Steven W. Johnson, head of the Parkinson Center of Oregon, said the study provides a greater understanding of the causes of Parkinson's disease.
"The use of a naturally occurring genetic mutation that is expressed by human dopamine neurons is a unique feature of this study," Johnson said. "Consequently, this study provides considerable support for the “dual hit” hypothesis that postulates that Parkinson’s disease may be the result of both genetic and environmental influences.
Source: U~T San Diego, 27 November 2013
http://www.utsandiego.com/news/2013/nov/27/parkinsons-pesticides-sanfor…
- Log in to post comments