American researchers conducted a series of experiments on mice and concluded that chronic exposure to the herbicide glyphosate causes symptoms of neuroinflammation and accelerates the progression of Alzheimer's disease in a model model, with these changes persisting long after exposure to the substance ceases. The study was published in the Journal of Neuroinflammation.
Glyphosate acts as a broad-spectrum, non-specific herbicide. Glyphosate-based products are the most popular weed control method worldwide. Furthermore, there are genetically modified crops—soybeans, corn, and cotton—that are resistant to glyphosate and designed to be grown in its presence, significantly increasing yields. Officially, this herbicide is considered low toxicity to humans: the World Health Organization and the Food and Agriculture Organization of the United Nations consider its acceptable daily intake to be up to a milligram per kilogram of body weight. However, there are concerns about the substance's potential carcinogenicity and other adverse effects, which require further research.
In 2022, Ramon Velazquez's team at Arizona State University demonstrated that glyphosate can penetrate the blood-brain barrier in mice and increase levels of the multifunctional proinflammatory cytokine tumor necrosis factor (TNF), which is involved in the pathogenesis of Alzheimer's disease, among other things. To test the herbicide's possible link to the development of this disease, the researchers used 3xTg-AD transgenic mice, which are inherently susceptible to the brain changes characteristic of this disease.
At 4.5 months of age, they began orally administering 3xTg-AD and normal animals 0, 50, or 500 milligrams of glyphosate per kilogram of body weight per day, continuing this for 13 weeks. At 12 months of age (approximately 4.5 months after exposure to the herbicide), the mice underwent a spatial memory test in the Morris water maze (by this time, 3xTg-AD exhibit significant deposits of beta-amyloid and tau protein in the brain). At 13.5 months (six months later), blood was collected from the animals and tissue preparations were made.
It was found that glyphosate administration did not affect the mice's body weight, but it did slightly increase the risk of premature death. In the water maze test, 3xTg-AD mice showed a dose-dependent tendency toward thigmotactic behavior (staying close to walls), indicating increased anxiety. Otherwise, the results were similar between the groups. Six months after administration, the herbicide metabolite aminomethylphosphonic acid was detected in brain samples.
After administration of both doses of glyphosate, the levels of proinflammatory cytokines and chemokines (eotaxin, granulocyte colony-stimulating factor, interferon-gamma, interleukin-9, CXCL1, and CCL4) were increased in the cerebral cortex of both normal and transgenic mice. The increase was more pronounced at the higher dose and in 3xTg-AD (in this group, an increase in cytokine and chemokine levels was also observed in the blood plasma). Also, in the brain of transgenic mice, after glyphosate administration, there was a significant increase in the levels of beta-secretase, which is involved in the formation of beta-amyloid; insoluble fractions of beta-amyloid-42; the size and number of plaques of this protein; and phosphorylated tau protein.
Thus, even after prolonged chronic exposure to glyphosate, pathological changes associated with neuroinflammation and accelerated progression of pathological changes characteristic of Alzheimer's disease are observed in the mouse brain. This suggests the need for further research into the toxicity of this popular herbicide, including in humans, the authors concluded.
The potential neurotoxicity of glyphosate is also supported by the results of a study of Ecuadorian adolescents. They showed that elevated levels of this substance in urine negatively impact neurobehavioral performance, especially when detected in combination with another popular herbicide, 2,4-dichlorophenoxyacetic acid.
