The herbicide linuron, commonly used with other herbicides, insecticides and fungicides to control the growth of grass and weeds, may be an important environmental risk factor in the development of neurological diseases that include multiple sclerosis, researchers suggest.
Used in the U.S. and other countries — but recently banned in Europe due to its potential health risks — this compound can promote pro-inflammatory signals in the central nervous system (brain and spinal cord) of mice with an MS-like disease, their study shows.
The study, “Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation,” was published in the journal Cell.
Genetics is widely recognized to influence the development of neurodegenerative disorders, contributing to about 64 percent of all MS cases. But evidence also suggests that the environment — both as a geographic place, and as what a person creates or does within the body through diet and other lifestyle choices — can significantly contribute to disease progression.
Inflammation is known to be the central biological mechanism involved in MS progression. But exactly how environmental factors may contribute is not clear.
A team led by researchers at Brigham and Women’s Hospital, affiliated with Harvard Medical School, developed a new way of identifying environmental factors that can boost immune-driven inflammation in the brain, as well as of defining signaling pathways involved in the regulation of immune-mediated pro-inflammatory activities.
“When we study inflammation and neurodegeneration, we learn that the environment may play just as important of a role as genetics,” Francisco Quintana, principal investigator in the Ann Romney Center for Neurologic Diseases at Brigham and senior study author, said in a press release.
The team used zebrafish embryos that were manipulated to have low levels of myelin protecting their nerve cells — similar to what happens in MS and other neurodegenerative diseases. The embryos were also genetically altered to produce a green fluorescent protein when potentially damaging signals were activated.
After a preliminary computer analysis of 976 molecules of the ToxCast chemical inventory — established by the U.S. Environmental Protection Agency (EPA), and including a collection of chemicals ranging from industrial and consumer products to food additives — the researchers selected 75 candidate compounds to explore further.
They exposed the zebrafish embryos to the different compounds, and identified five that triggered production of the fluorescent protein in the central nervous system. They also tested both linuron and methyl carbamate (used by the textile, polymer, and pharmaceutical industries) in key brain and spinal cord cells from mice, called astrocytes, and recorded inflammatory increases within these cells.
Further experiments in mice with experimental autoimmune encephalomyelitis (EAE), a condition that mimics many clinical features of MS, showed that blocking the signals triggered by linuron effectively prevented these key nervous system cells from activating.
These findings also seemed to translate in ways possibly relevant to people. The team evaluated tissue samples collected from MS patients and healthy controls. They found that patient samples, from brain lesions and normal-appearing white matter, had higher-than-usual levels of linuron-associated signals, suggesting these signals contribute to MS progression.
“Our findings support the need for systematic investigation of the effects of the ‘exposome’— all of the environmental exposures people experience in their lifetime — on neurologic diseases and other conditions,” Quintana said. “Studies of the exposome have the potential to identify unknown origins of inflammation and key environmental factors that may contribute to risk.”
The team emphasized that epidemiological studies are needed to further evaluate how these compounds affect humans.
“This strategy may guide future epidemiologic studies of the effects of the environment on neurologic diseases while identifying molecular mechanisms that control central nervous system pathology and potential therapeutic targets for MS and other neurologic diseases,” the researchers wrote.