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News in Brief
Scientists have confirmed a long-standing hypothesis that too much dopamine inside certain brain cells leads to the cell death that causes Parkinson’s disease (PD). However, whether neurons die also depends on calcium levels and the presence of the protein alpha-synuclein. The study, led by Eugene V. Mosharov, Ph.D., and David Sulzer, Ph.D., of Columbia University, appeared in the April 30 edition of the journal Neuron.
Investigators asked the question: what are the features of dopamine neurons in PD that make them susceptible to cell death? Using a novel procedure called intracellular patch electrochemistry, they determined that dopamine cells in PD have elevated levels of dopamine floating free within them, higher than normal calcium levels and an accumulation of the protein alpha-synuclein.
As researchers predicted, the elevated levels of the so-called cytosolic dopamine were toxic to neurons. Decreasing these levels, either genetically or by using drugs, successfully prevented cell death. Alternatively, even with high dopamine levels, decreasing the level of calcium was also protective. And cells that lacked alpha-synuclein were more resilient against elevated dopamine than those that contained the protein.
Researchers concluded that it takes a combination of biological factors all happening at the same time in order to cause dopamine neurons to die. Therapies aimed at interfering with any one of these processes could, in theory, be neuroprotective.
Drs. Mosharov and Sulzer are both supported through PDF’s annual Center Grant to Columbia University.
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Prolonged exposure to two widely-used pesticides — maneb and paraquat — may put a person at a higher risk of developing Parkinson’s disease. This risk is elevated if the exposure occurs earlier in life, according to a report in the April 15 issue of the American Journal of Epidemiology.
Authors Beate Ritz, M.D., Ph.D., and her colleagues from the University of California, Los Angeles (UCLA) performed a study involving residents of California’s Central Valley, an area known for its wide exposure to agricultural pesticides. Little research has been conducted on how pesticides affect people because it is difficult to accurately estimate exposure. To solve this problem, her team developed a “geographic information systems” tool that allowed them to correlate pesticide use from 1974-1999, locations of farmland, residences of people with PD and controls, and more, onto a single map for analysis. Using the tool, they identified residential areas that would have been exposed to maneb and paraquat over the 25 year period.
Of the 709 people who were enrolled in the study, 368 had been diagnosed with PD within the past three years and had lived in one of three counties in Central Valley for at least five years. The remaining 341, who served as a control group, did not have PD, but had also lived in the same geographic area for at least five years.
Researchers found that when people were exposed to both maneb and paraquat within 500 meters of their homes, their likelihood of being diagnosed with PD was substantially increased as compared to those without exposure. The majority of the risk for being diagnosed with PD was attributed to those individuals exposed between 1974 and 1989 — all of whom were children, teenagers or young adults at the time. This group of people, who had younger-onset PD — meaning that they were diagnosed before the age of 60 — were up to four to six times more likely to develop PD if they were exposed to both pesticides.
For years, there have been anecdotal observations that Parkinson’s is found in higher rates among farmers and in rural populations. This study provides epidemiological support for an association between pesticide exposure and Parkinson’s, and fits with previous scientific models in animals, in which pesticides cause a loss of dopamine brain cells. Epidemiological studies of this type, however well designed, are based on retrospective estimates of toxin exposure and are subject to error. While most individuals who are exposed to pesticides will not develop PD, this study is important because it is the first to suggest that two pesticides can work together to increase a person’s risk for PD, and to demonstrate that those most at risk are people with younger-onset PD who were exposed at a young age.
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