Chemicals on the Brain

Scientists are close to discovering how environmental factors could cause some people to develop Parkinson’s disease.

By Sarah Parsons

When it comes to disorders affecting the brain, Parkinson’s disease (PD) ranks among the most enigmatic. Despite decades of research, scientists still can’t pinpoint what causes the disease, and no cure exists. This lack of understanding is particularly problematic because of the disease’s relatively high prevalence: It is the most common neurodegenerative disorder after Alzheimer’s, with 160,000 new diagnoses in the US each year.

Parkinson’s disease causes cell death in a section of the midbrain called the substantia nigra. The cell death in turn results in a loss of the chemical dopamine, a neurotransmitter. PD symptoms like tremor, slowness of movement, rigidity, and poor balance do not typically appear until about 60 percent of the dopamine neurons are lost, making early diagnosis virtually impossible. While about five percent of cases are caused by “familial PD” (inherited from family members), the vast majority are attributed to “sporadic PD”—likely the result of an unknown combination of genetic susceptibility and environmental influences. Though scientists have yet to discover a method to diagnose PD before significant cell damage occurs, they are getting close to understanding the factors that affect its development. Recent studies—including one published today in the Journal of Neuroscience—suggest that some of PD’s main triggers may be toxins in the environment.

The latest study, conducted by the Buck Institute for Age Research in Novato, CA, looked at how two environmental agents affect PD development in mice. Previous research suggested that excess iron intake during infancy and exposure to certain herbicides later in life increased the likelihood of developing PD. But the Buck Institute study took this knowledge one step further: Researchers fed mice excess iron during the neonatal period and exposed them to the herbicide paraquat (a weed killer used on fruit orchards and plantation crops) at various points during their life cycle, and analyzed the toxins’ effects in the context of aging.

“When we combined neonatal iron feeding with paraquat exposure and looked over the lifespan of the animal, we saw that these environmental factors were additive in terms of the amount of dopaminergic cell loss they caused, and that it seemed to be an age-dependent effect,” says Julie Andersen, the lead author of the study. “Broadly this suggests that susceptibility for PD is age dependent, and may depend on the environmental agents that you’re exposed to over your lifespan.”

The study supports a mounting body of evidence that environmental factors heavily influence whether or not a person will develop PD.

“The best of what we know in Parkinson’s disease is that the environmental component plays as much if not a greater role than the genetic component,” says Donato Di Monte, the director of basic research at The Parkinson's Institute in Sunnydale, CA.

Epidemiological evidence also seems to suggest that environmental factors are important. For example, Andersen says that people who live in rural environments and drink well water, and others who handle pesticides regularly report a higher incidence of the disease.

Buck Institute researchers reported another finding as well: Scientists treated one group of mice with an antioxidant, EUK-189, while also exposing mice to toxins. They found that mice given the antioxidant endured less cell death than those who were just given toxins.

While this information offers new insight into possible treatments, scientists agree that they must first develop an early diagnostic method for PD before neuron degeneration can be prevented.

“By the time somebody’s showing symptoms, they’ve already lost like 60 percent of the dopaminergic neurons,” says Andersen. “We really need to have an early diagnostic marker so we can catch this neuronal cell loss well before it’s that extensive.”

But before that happens, scientists must first learn more about how exposure to certain chemicals and elements might trigger the disease.

“More research needs to be focused on the environment because there is so much evidence suggesting that environmental factors play a role in the disease,” says Di Monte. “Being able to identify these factors could have a tremendous impact on our ability to prevent and identify as early as possible.”

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