Halting the Rise of Parkinson’s

Quality of life, health, and longevity are being increasingly tied to someone’s zip code rather than their genetic code. Cancer, heart disease, neurodegenerative disorders, and even our ability to fight infection are linked to the myriad of chemicals we are exposed to, often unwittingly, over the course of our lives. The University of Rochester’s leadership in the field of environmental medicine stretches back to toxicology research programs developed at the University under the Manhattan Project. These programs also served as the basis for the formation of a NIEHS Center of Excellence in environmental toxicology and health that is one of the oldest in the country celebrating 50 years of sustained funding. This foundation and the decades of work that followed—coupled with the recognition that the public health threat requires a collaborative commitment to research, education, and community engagement—led to the creation of the new Institute for Human Health and the Environment.

Paige Lawrence, PhD, the Wright Family Research Professor and chair of the Department of Environmental Medicine, is the founding director of the new Institute. “Genetics only explaining 10 to 15 percent of human health, which leaves the rest to the environment,” said Lawrence. “If we really want to have an impact on health, environmental influences need to be front and center.”

The new Institute will help power a team of neurologists, neuroscientists, toxicologists, epidemiologists, and researchers at the University of Rochester who are examining the impact of environmental chemical exposure on the brain. One disease in particular stands out. Parkinson’s is the fastest growing neurodegenerative disease in the world, outpacing even Alzheimer’s, and a growing number of scientists are linking the disease’s rise to air pollution, pesticides, and a ubiquitous chemical pollutant.

Up the nose it goes

Air pollution is associated with many health problems, including asthma, heart disease, stroke, low birth weight, and inflammation. While epidemiological studies have hinted at the link between air pollution and neurological disorders like Parkinson’s and Alzheimer’s, the route these chemicals use to make their way into the brain, and the damage caused once there, was until recently poorly understood.

“We’ve known that air pollution has effects on the heart and the lung for a very long time, but it's really only been in about the past ten years that attention has been directed to its effects on the brain,” said Debbie Cory-Slechta, PhD, a professor of Environmental Medicine, Neuroscience, and Public Health Sciences. Cory-Slechta’s colleagues at the University of Rochester, Guenter Oberdoerster, PhD, and Alison Elder, PhD, were among the first to show that ultra-fine air pollution particles, called PM0.1, are able to hitch a ride directly into the brain via the nasal passage and olfactory nerves, bypassing the brain’s normal defenses.

Researchers are quick to point out that many challenges hinder the field of air pollution research, including the fact that they suspect damage to the brain is caused not by a single component but rather multiple different chemicals acting together. “Air pollution is a very complicated exposure,” said Cory-Slechta. “It is comprised of a mixture of gases and particles, and those particles carry other metals and organic toxins into the brain.”

Another factor is that several decades can pass between exposure and onset of symptoms, making the time, place, and “dose” of exposure difficult to identify. Unlike other forms of air pollution, there is not widespread and routine monitoring for ultra-fine particles. Furthermore, exposure could be more dangerous for individuals already at higher risk for diseases like Parkinson’s, or when the exposure occurs during important, and vulnerable, development stages.

Modeling human exposure

This last question is one of the areas of focus of the lab of Marissa Sobolewski, PhD, an assistant professor of Environmental Medicine who is studying how a wide range of environmental pollutants—including those found in air pollution—act as endocrine active chemicals. These chemicals can disrupt normal hormonal function in newborns and mothers, potentially setting the stage for neurological and behavioral disorders later in life.

Her lab is also conducting experiments that model exposure to ultra-fine iron particles. This research project arose out of findings that showed that the air in some parts of the New York City subway system contain iron particles at levels 30 times higher than safe levels established by the EPA. Sobolewski points to this project as an example of the translational focus of her lab’s work.

“When we're trying to understand the influence of pollution on the brain and behavior, it is important that we are appropriately modeling the environmental toxic exposure and making our animal model as translationally relevant to what people are being exposed to in the everyday world,” said Sobolewski.

A key research tool that enables these studies is the Inhalation Exposure Facility at the University of Rochester, which can trace its origins to the Manhattan Project. The current facility brings together researchers in fields such as biology, chemistry, and physics to support research into how airborne agents, by themselves or in combination with other factors, contribute to cumulative health risk across the lifespan.

Cory-Slechta and Sobolewski are frequent collaborators and recently co-authored a commentary piece in Nature Reviews Neuroscience pointing to the concerning and growing body of research linking air pollution to neurological disorders and calling for more stringent and targeted regulation of the sources of air pollution.

Parkinson’s is a global public health crisis

When James Parkinson first described the disease that bears his name in 19th century London, he reported six individuals with the disease. “Two hundred years later, the global burden of disease is now estimated to be more than 6 million people,” said Ray Dorsey, MD, the David M. Levy Professor of Neurology at the University of Rochester and co-author of the book “Ending Parkinson’s Disease”. “The rates are growing far faster than aging could explain alone. It has to be environmental factors and air pollution, pesticides, and industrial chemicals are all important contributors.”

The chemical burden contributing to Parkinson’s rise is a byproduct of industrialization, in the form of ongoing pollution and the toxic legacy of contaminated sites, as well as the introduction of synthetic chemicals for agricultural use. The association between Parkinson’s and industrial growth is strong. Countries that have experienced the least industrialization have the lowest rates of the disease, whereas those undergoing the most rapid transformation, such as China, have the highest rates of increase.

Paraquat, a widely used and highly toxic herbicide, and other pesticides are increasingly being linked with Parkinson’s disease. A landmark study in 2011 showed that occupational exposure to paraquat increases Parkinson’s risk by 150 percent. More recently, research by Cory-Slechta and Sobolewski published last year in the journal Toxicological Sciences shows that paraquat can enter the brains of mice via the olfactory nerve.

Safety concerns have led to the banning of paraquat in more than 30 countries. However, its domestic use continues to rise unabated and the weed killer is applied to millions of acres annually to aid the production of soybeans, corn, cotton, and other crops.

An investigative report published in the British newspaper The Guardian last year details how for decades paraquat’s manufacturer downplayed the chemical's toxic effects, hid its own research results, and discredited the work of other scientists. One of the scientists targeted by the company was Cory-Slechta, who was one of the first to show that paraquat killed dopamine-producing neurons in mice, hinting at its role in Parkinson’s disease. Internal documents show the company worked behind the scenes in 2005 to block her from serving on an Environmental Protection Agency’s (EPA) scientific advisory committee on pesticides. “Rather than remove this dangerous chemical from the market or develop a safer alternative, the company doubled down on its blockbuster product and sought to expand its use,” said Dorsey, who argues that the U.S. should join the European Union, UK, and China to ban paraquat.

A ubiquitous pollutant

For the last 100 years, the industrial solvent trichloroethylene (TCE) was widely used in a number of industrial, consumer, military, and medical applications, including to decaffeinate coffee, degrease metal, and dry-clean clothes. Its use in the U.S. peaked in the 1970s, when more than 600 million pounds of the chemical—or two pounds per American—were manufactured annually.

Countless Americans are exposed to the chemical through contaminated groundwater, drinking water, and indoor air pollution. TCE is found in half of the most toxic EPA Superfund sites and numerous military bases, including Camp Lejeune in North Carolina, where a million Marines, their families, and civilians were exposed to the chemical in drinking water over a three-decade period. A growing body of epidemiological and lab-based research are linking TCE to Parkinson’s disease.

Dorsey and URMC neurologists Ruth Schneider, MD, and Karl Kieburtz, MD, recently co-authored a piece in the Journal of Parkinson’s Disease pointing to TCE as an invisible cause of Parkinson’s. They call for urgent action: accelerated remediation, containment, and mitigation of contaminated sites; more research to understand how TCE contributes to Parkinson’s and other diseases; closer monitoring and disclosure of TCE levels in groundwater, drinking water, soil, and outdoor and indoor air; and banning TCE and its close chemical cousin perchloroethylene (PCE) in the U.S.

“The world’s fastest-growing brain disease may be largely preventable,” said Dorsey. “Pesticides are likely to blame for those who grew up in or live in rural areas, and industrial chemicals like TCE may be to blame in urban areas. Banning these toxic chemicals, containing contaminated sites and protecting homes, schools, and buildings at risk may all help create a world where Parkinson’s is increasingly rare, not common.”