A toxin that travels from stomach to brain may trigger Parkinsonism

December 4, 2018, Pennsylvania State University
Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

Combining low doses of a toxic herbicide with sugar-binding proteins called lectins may trigger Parkinsonism—symptoms typical of Parkinson's disease like body tremors and slowing of body motions—after the toxin travels from the stomach to the brain.

In a study with rats, researchers at Penn State College of Medicine found that after ingesting paraquat, a once widely used herbicide that has been banned in the U.S. since 2007, along with lectins—sugar-binding proteins found widely in nature—the animals developed Parkinsonism.

According to Thyagarajan Subramanian, professor of neurology and neural and behavioral sciences and co-author on the study, the findings—recently published in the journal Parkinson's Disease—offer clues to how and why Parkinson's disease develops, and offer a model to test new medications in the future.

"This study gives solid evidence that lectins, while in the presence of certain toxins, may be one potential culprit for the cause of Parkinsonism," Subramanian said. "Additionally, this can be a tool in the future to continue developing new medications and treatments for Parkinson's disease."

The researchers were able to track the formation and spread of a misfolded protein called alpha-synuclein, which previous research has linked with Parkinson's.

"We were able to demonstrate that if you have oral paraquat exposure, even at very low levels, and you also consume lectins—perhaps in the form of uncooked vegetables, dairy or eggs—then it could potentially trigger the formation of this protein alpha-synuclein in the gut," Subramanian said. "Once it's formed, it can travel up the vagus nerve and to the part of the brain that triggers the onset of Parkinson's disease."

R. Alberto Travagli, professor of neural and and senior author of the study, said that while toxins like paraquat have been suspected of contributing to Parkinson's for decades, the scientific evidence was small. While paraquat was linked with Parkinsonism in previous studies, those experiments typically used high doses of paraquat that humans were not likely to encounter in real life.

Additionally, lectins, which are used in medications to help deliver substances into the brain or stomach, also have been associated with certain rare forms of Parkinsonism. But the researchers weren't sure if it was the lectins themselves that were causing Parkinsonism, or if they were helping different substances get into the body that then triggered the symptoms.

"Experimenting with the lectins together with the toxin makes sense, because lectins are used in pharmacology to chaperone other substances into the body," Travagli said. "So it makes sense that the two can be combined and used to make the toxicity more potent, even though the amount of toxin is very low."

Using a rat model, the researchers exposed the animals daily to small doses of paraquat and lectins for seven days. After stopping the treatment, the researchers waited two weeks. Then, the researchers did a variety of tests to measure problems with motor function and other symptoms typical of Parkinsonism.

The researchers observed a decrease in that was consistent with Parkinsonism. But to confirm that the symptoms were related to Parkinsonism and not another cause, Travagli said he and the other researchers did several additional tests.

"After observing that these animals did indeed show symptoms of Parkinsonism, we wanted to double check and make sure we weren't looking at animals that had these symptoms for another reason," Travagli said. "We administered levodopa, which is a common medication for Parkinson's disease. We saw a return to almost normal types of motor responses, which was a clear indication that we were looking at some sort of Parkinsonism."

Additionally, the researchers said when the vagus nerve was disconnected from the stomach prior to exposure to paraquat and lectins, the animals were protected from Parkinsonism, confirming the route of the from the gut to the brain.

In the future, Travagli and Subramanian said they will explore whether interventions in the form of diet modifications or medications that interfere with the transport of alpha synuclein from the stomach via the could be used to help prevent or slow the development of Parkinsonism in this rat model. This includes a natural substance called squalamine which has been shown to remove alpha synuclein from the gut and is now in clinical trials for the certain symptoms associated with Parkinson's disease.

Explore further: Unravelling the biology of parkinsonism

More information: L. Anselmi et al, Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat, npj Parkinson's Disease (2018). DOI: 10.1038/s41531-018-0066-0

Related Stories

Unravelling the biology of parkinsonism

August 22, 2016
Scientists have taken another step towards understanding the causes of parkinsonism by identifying what's happening at a cellular level to potentially help develop future treatments.

Study says life span normal when Parkinson's does not affect thinking

October 31, 2018
In the past, researchers believed that Parkinson's disease did not affect life expectancy. But recent studies showed a somewhat shorter life span. Now a new study suggests that when the disease does not affect thinking skills ...

Half of women to develop stroke, dementia, or parkinsonism

October 25, 2018
(HealthDay)—One in two women and one in three men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online Oct. 1 in the Journal of Neurology, Neurosurgery & Psychiatry.

Shedding a tear may help diagnose Parkinson's disease

February 22, 2018
Tears may hold clues to whether someone has Parkinson's disease, according to a preliminary study released today that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to ...

Study raises doubts on a previous theory of Parkinson's disease

July 6, 2018
Parkinson's disease was first described by a British doctor more than 200 years ago. The exact causes of this neurodegenerative disease are still unknown. In a study recently published in eLife, a team of researchers led ...

Parkinson's: Newly discovered antibody could facilitate early diagnosis

July 20, 2012
Conditions such as Parkinson’s disease are a result of pathogenic changes to proteins. In the neurodegenerative condition of Parkinson’s disease, which is currently incurable, the alpha-synuclein protein changes ...

Recommended for you

Two compounds in coffee may team up to fight Parkinson's

December 10, 2018
Rutgers scientists have found a compound in coffee that may team up with caffeine to fight Parkinson's disease and Lewy body dementia—two progressive and currently incurable diseases associated with brain degeneration.

New Parkinson's disease drug target revealed through study of fatty acids

December 4, 2018
The human brain is rich in lipids. Investigators studying Parkinson's disease (PD) have become increasingly interested in lipids since both molecular and genetic studies have pointed to the disruption of the balance of the ...

A toxin that travels from stomach to brain may trigger Parkinsonism

December 4, 2018
Combining low doses of a toxic herbicide with sugar-binding proteins called lectins may trigger Parkinsonism—symptoms typical of Parkinson's disease like body tremors and slowing of body motions—after the toxin travels ...

Experimental cancer drug shows promise for Parkinson's

December 3, 2018
The study, funded by Parkinson's UK, suggests that the drug, tasquinimod, which is not yet on the market, works by controlling genes that may cause Parkinson's. This happens when the drug interacts with a protein inside brain ...

Parkinson's therapy creates new brain circuits for motor function, study finds

November 28, 2018
Scientists have uncovered that an emerging gene therapy for Parkinson's disease creates new circuits in the brain associated with improved motor movement. These findings, published today in Science Translational Medicine ...

The puzzle of a mutated gene lurking behind many Parkinson's cases

November 15, 2018
Genetic mutations affecting a single gene play an outsized role in Parkinson's disease. The mutations are generally responsible for the mass die-off of a set of dopamine-secreting, or dopaminergic, nerve cells in the brain ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.