American researchers conducted a series of experiments on mice and came to the conclusion that chronic intake of the herbicide glyphosate causes symptoms of neuroinflammation and accelerates the development of Alzheimer's disease when modeled, and these changes persist for a long time after contact with the substance ceases. A report on the work was published in the Journal of Neuroinflammation.
Glyphosate acts as a broad-spectrum non-specific herbicide. Products based on it are the most popular method of weed control in the world. In addition, there are genetically modified crops: soybeans, corn and cotton, which are resistant to glyphosate and designed to be grown in its presence, which significantly increases yields. Officially, this herbicide is considered low-toxic to humans: the World Health Organization and the Food and Agriculture Organization of the United Nations consider its permissible daily intake to be up to a milligram per kilogram of body weight. However, there are concerns about possible carcinogenicity and other negative effects of the substance, which require additional research.
In 2022, Ramon Velazquez's group at Arizona State University showed that glyphosate can cross 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 possible connection between the herbicide and the development of this disease, the researchers used transgenic 3xTg-AD mice, which are innately susceptible to the characteristic changes in the brain.
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 for 13 weeks. At 12 months of age (approximately 4.5 months after exposure to the herbicide), the mice were tested for spatial memory in the Morris water maze (by this time, 3xTg-AD show significant deposits of beta-amyloid and tau protein in the brain). At 13.5 months (six months later), blood was taken from the animals and tissue preparations were made.
It turned out that glyphosate administration did not affect the body weight of the mice, but slightly increased the chances of premature death. In the water maze test, 3xTg-AD showed a dose-dependent tendency toward thigmotactic behavior (staying close to the walls), indicating increased anxiety. Otherwise, the results were similar between the groups. Six months after the herbicide administration, its 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, with the increase being more pronounced at the higher dose and in 3xTg-AD (in this group, an increase in the level of cytokines and chemokines was also observed in the blood plasma). Also, in the brain of transgenic mice after administration of glyphosate, 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, as well as phosphorylated tau protein, significantly increased.
Thus, even after a long period of chronic exposure to glyphosate, pathological changes associated with neuroinflammation and accelerated progression of pathological changes characteristic of Alzheimer's disease are observed in the brain of mice. This indicates the need for further research into the toxicity of the popular herbicide, including for humans, the authors of the study concluded.
Glyphosate's potential neurotoxicity is also supported by a study of Ecuadorian adolescents. They found that elevated levels of the substance in urine negatively impacted neurobehavioral performance, especially when it was found in combination with another popular herbicide, 2,4-dichlorophenoxyacetic acid.
