New research reveals how the pesticides paraquat and maneb alter gene expression and may lead to Parkinson's disease in people who are genetically predisposed to the illness.
Although it is not exactly known what causes the disease, both genetic and environmental factors are thought to play a critical role.
The National Institutes of Health (NIH) note that environmental exposure to pesticides, for example, might increase the risk of developing Parkinson's.
Older studies have suggested that the pesticides paraquat and maneb, in particular, may increase vulnerability to Parkinson's in people who are already genetically prone to developing the illness.
More recent studies have sought to unpack the neuronal mechanisms that are at play in this link between pesticides and the neurodegenerative condition.
For instance, some studies have shown that pesticides interfere with neurogenesis — the process wherein the brain creates new neurons — in the hippocampus, which is a key brain region for memory and information processing.
Pesticides have this effect by causing genetic alterations. Now, a new study by researchers at the University of Guelph (U of G) in Ontario, Canada, unravels some of the ways in which pesticides cause genetic mutations, leading to neurodegeneration.
Senior study author Scott Ryan, a professor of molecular and cellular biology at U of G, explains the motivation behind the research. He notes, "People exposed to these chemicals are at about a 250 percent higher risk of developing Parkinson's disease than the rest of the population."
"We wanted to investigate what is happening in this susceptible population that results in some people developing the disease," Prof. Ryan adds.
The findings were published in the journal Federation of American Societies for Experimental Biology.
One of the first studies to look at human cells
At least 30 alterations in this gene have been associated with Parkinson's, and α-synuclein protein clumps are a well-documented, albeit poorly understood, hallmark of the disease.
For the new research, the scientists also worked with normal embryonic cells that they modified using genetic editing to replicate the α-synuclein genetic mutation.
Prof. Ryan explains why using human cells makes this study particularly valuable. "Until now," he says, "the link between pesticides and Parkinson's disease was based primarily on animal studies as well as epidemiological research that demonstrated an increased risk among farmers and others exposed to agricultural chemicals."
"We are one of the first to investigate what is happening inside human cells," explains Prof. Ryan.
Stem cells are undifferentiated cells that go on to individualize into specific types of cells. Prof. Ryan and his colleagues used the two types of stem cells to derive dopamine-producing nerve cells from them.
Then, they exposed these dopaminergic neurons — which are known to be affected the most by Parkinson's disease — to the two pesticides.
Pesticides deplete neurons of energy
It was found that the neurons that had been exposed to the chemicals had faulty mitochondria.
Mitochondria, also known as the "powerhouses of the cell," are the organelles inside a cell that turn sugar, fats, and proteins into the energy our body needs to survive and function.
But this study demonstrated that the mitochondria inside the dopamine neurons affected by pesticides could not move freely as they normally would. This "sucked" the energy out of the neurons.
Importantly, the levels of chemicals used to impair these neurons were below the ones deemed "lowest observed adverse effect level" by the United States Environmental Protection Agency (EPA).
Prof. Ryan says that this means we should re-evaluate EPA's guidelines for these two pesticides.
"This study shows that everyone is not equal, and these safety standards need to be updated in order to protect those who are more susceptible and may not even know it," he adds.
"People with a predisposition for Parkinson's disease are more affected by these low-level exposures to agrochemicals and therefore more likely to develop the disease."
Prof. Scott Ryan
"This is one of the reasons," he concludes, "why some people living near agricultural areas are at a higher risk.