University of Rochester scientists investigating the link between PCBs, pesticides and Parkinson's disease demonstrated new and intricate reactions that occur in certain brain cells, making them more vulnerable to injury after exposures.
In two papers published in the journal NeuroToxicology (Dec. 2004 and Feb. 2005), the group describes how polychlorinated biphenyls (PCBs) disrupt dopamine neurons, which are the cells that degenerate during the course of Parkinson's disease. Researchers also show that low levels of maneb, a fungicide commonly used in farming, can injure the antioxidant system in those same types of cells. Environmental contaminants might make dopamine cells more vulnerable to damage from normal aging, infection, or subsequent exposure to pollutants, researchers say.
The investigation is part of a nationwide race to better understand every aspect of Parkinson's disease, which affects up to 1 million Americans. It is a progressive neurological disorder that occurs when certain nerve cells in the substantia nigra region of the brain die or can no longer produce the brain chemical dopamine. A lack of dopamine is what causes patients to experience tremors, stiffness in the limbs and trunk, and impaired movement or balance.
In the 1990s scientists reported that the brains of Parkinson's patients contained elevated levels of PCBs and certain pesticides. While researchers believe that genetics, the aging process and exposure to toxicants all play a role in the development of Parkinson's, the group led by Lisa Opanashuk, Ph.D., is focused on environmental exposures. The National Institute of Environmental Health Sciences is funding the work.
"If we can identify the mechanisms by which PCBs or pesticides perturb dopamine neuron function, it may lead to the development of therapies that can prevent, slow or stop the progression of Parkinson's," says Opanashuk, an assistant professor of Environmental Medicine.
PCBs create havoc in the body's cellular system by producing free radicals, which leads to a process known as oxidative stress (OS). Oxidative stress is thought to be one of the main causes of cell degeneration. Normally, antioxidants can balance the damage done by OS. But toxic pesticide exposure, combined with the normal aging process, shifts the equilibrium toward oxidative stress and neurodegeneration.
The Rochester studies demonstrate, for the first time, the intricate OS and antioxidant responses to PCBs in dopamine neurons. Investigators treated dopamine cells and other brain cells with PCBs and documented the activation of oxidative-stress related pathways. Further research will evaluate how PCBs become risk factors for disease.