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Finding the Triggers for Parkinson’s Disease Environmental engineer Kurt Pennell is investigating how pesticides and other common chemicals may linger in the brain and spur the illness on By Marjorie Howard Could common chemicals play a role in triggering Parkinson’s disease? It’s a distinct possibility, says Kurt Pennell, professor and chair of civil and environmental engineering. Parkinson’s disease, a degenerative disorder of the central nervous system, results in resting tremors, stiffness and loss of movement. Efforts to identify its genetic cause have met with limited success, accounting for less than 10 percent of the known Parkinson’s cases. That has led researchers to consider environmental culprits. Pennell suspects that that persistent organic pollutants, such as pesticides, insecticides and other chemicals that remain in the environment and linger in the body long after exposure, play a role in the onset and progression of Parkinson’s disease. “Our brains are particularly vulnerable because of their limited antioxidant capacity,” says Kurt Pennell. Photo: Joanie Tobin One of those chemicals is rotenone, a “natural” pesticide once widely used in organic farming, because it was believed to be safe. Instead, it has been shown in laboratory studies to induce Parkinson’s-like symptoms. Like other chemicals that Pennell studies, including PCBs and dieldrin, which was developed as an alternative to DDT, rotenone is hydrophobic, meaning it is not attracted to water and instead is drawn to fat, where it is stored. The human brain, which is two-thirds fat, is therefore a prime target for storing the chemical. Scientists don’t think these chemicals directly cause Parkinson’s, a long-term disease that progresses very slowly. Rather, “having this exposure or having these chemicals in your system may increase the rate at which you start to have symptoms,” says Pennell. “So you may have them at a younger age or they may progress more rapidly.” Pennell says the presence of these compounds in the brain increases oxidative stress, a state in which the body is less able to fend off free radicals, which cause damage to the brain and to the body. Antioxidants are molecules that counteract the free radicals. “Our brains are particularly vulnerable because of their limited antioxidant capacity and potential for radical formation,” says Pennell. “We suspect that the presence of these compounds in the brain alters how dopamine is packaged and increases oxidative stress within neurons, meaning it could both predispose people to Parkinson’s and also accelerate the disease.” Dopamine is a chemical that acts as a neurotransmitter. In patients with Parkinson’s disease, dopamine-containing neurons located in the midbrain are damaged and eventually die, which reduces their ability to control movements. Pennell conducts his research in conjunction with the Collaborative Centers for Parkinson’s Disease Environmental Research at Emory University. “We expose animals to dieldrin, PCBs and other chemicals, and look at their response to that exposure,” he explains. “We look for markers of oxidative stress in the brain and for concentrations of chemicals in their tissue and in their blood. I measure the amount of chemicals and how long it persists in the body.” Pennell says the animals are given low concentrations of chemicals in an effort to mimic dose levels that might be found in the environment. In the last decade scientists have begun to accept the idea that common chemicals can spur Parkinson’s along, says Pennell, but more studies, such as the ones he is conducting, are needed to prove it, and help understand relationships between chemical exposures, genetic predisposition and lifestyle factors in Parkinson’s disease. In addition, the ways in which oxidative stress contribute to nerve degeneration are not well understood. “We’d like to identify biomarkers that may indicate that someone is more susceptible to oxidative stress and eventually find therapies for people who have been exposed to these chemicals.” Tiny Particles, Big Questions Pennell is also interested in finding out whether oxidative stress might be caused by nano materials, manufactured particles that are less than one millionth of a meter in size. Because they are so tiny, monitoring their use and disposal is challenging, and there are concerns they are escaping into the environment and may pose a health hazard. Nanotechnology, which involves the use of these tiny particles, allows researchers to work on a molecular level. Nano-sized materials are 1/100 nanometers in diameter. For scale, think about it this way: a sheet of paper is about 100,000 nanometers thick. The use of nano materials, says Pennell, has become increasingly common in products such as sunscreen and cosmetics and in medical applications such as imaging. And scientists predict nanotechnology will also be used in manufacturing, such as for aircraft, buildings and automobiles, taking advantage of its lightweight properties. In health care, nanotechnology is used when precision is key, such as delivering the right amount of medicine to the exact location in the body where it is needed most. But the consequences of using such tiny materials are unknown, since it is uncertain what effect they have on the environment and on the human body. There are concerns that nano materials could be discharged from industrial plants into waterways or accidentally released into the air during their production. Researchers are wondering if they may cause brain damage, resulting in such diseases as Parkinson’s. Researchers need to understand how nano materials behave so they can learn how to better control them, says Pennell. In one project, he studies how carbon- based nanoparticles move in water. He and Linda Abriola, dean of the school of engineering, recently received a $350,000 grant from the National Science Foundation to study the effects of metal-based nanoparticles on both the body and the environment. “No one really knows what happens if we release nanoparticles into the environment—what happens and where are they going to go,” says Pennell. “How will they be transported and retained? What happens if they reach a body of water or if they’re spilled or put into a dump? We need to understand how to control them.” http://tuftsjournal.tufts.edu/2010/03_1/features/01/ ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn