New study reveals glyphosate's hidden dangers: persistent brain inflammation, anxiety, and Alzheimer's-like damage in mice, even months after exposure.
Study: Glyphosate exposure exacerbates neuroinflammation and Alzheimer’s disease-like pathology despite a 6-month recovery period in mice. Image Credit: wellphoto / ShutterstockStudy: Glyphosate exposure exacerbates neuroinflammation and Alzheimer’s disease-like pathology despite a 6-month recovery period in mice. Image Credit: wellphoto / Shutterstock
In a recent study published in the Journal of Neuroinflammation, researchers investigated the effects of 13 weeks of daily oral glyphosate exposure on 4.5-month-old female 3xTg-AD and NonTg mice, followed by a six-month recovery period. Their findings revealed that both glyphosate and its primary metabolite, aminomethylphosphonic acid (AMPA), persisted in the brain tissue and peripheral blood of the mice despite the extended recovery period.
Concentrations of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), a hallmark of Alzheimer's Disease (AD) pathophysiology, were significantly elevated in exposed mice. Behavioral tests revealed increased anxiety-like behavior, while brain tissue analyses showed exacerbated AD-like neuropathologies, including heightened levels of amyloid-β and phosphorylated tau. Importantly, the study also found that mortality was higher in 3xTg-AD mice regardless of glyphosate dosage, but this trend was not dose-dependent.
Background
Environmental Persistence: Glyphosate's metabolite aminomethylphosphonic acid (AMPA) can persist in soil and aquatic environments for months, with soil type and environmental conditions influencing its breakdown and mobility.
Alzheimer's Disease (AD) is a neurodegenerative disorder that causes a progressive decline in patients' memory recall, cognitive function, and ability to perform routine daily tasks. Global AD prevalence is rising rapidly. In the United States alone, more than 6.7 million individuals live with the condition, and this number is projected to reach 14 million by 2060. Decades of research suggest that environmental exposures, notably pollution (air), behaviors (diet, sleep), certain infections, and toxin exposure, contribute substantially to AD risk and progression.
Glyphosate (N-(phosphonomethyl) glycine) is the most widely used herbicide in the world, with approximately 300 million pounds applied annually in the United States alone. The World Health Organization (WHO) classifies glyphosate as "possibly carcinogenic to humans," while the U.S. Environmental Protection Agency (EPA) controversially maintains that it poses no risks to human health. Despite this, growing evidence highlights glyphosate's adverse effects on human health, including its ability to cross the blood-brain barrier (BBB) and potentially disrupt neuroimmune mechanisms.
About the Study
The study aimed to elucidate the impacts of two glyphosate concentrations (50 mg/kg and 500 mg/kg) compared to a control group (0 mg/kg) on murine survival and AD-like neuropathologies. Researchers used female 3xTg-AD homozygous mice as cases (n = 42), alongside NonTg controls (n = 45). Behavioral and biochemical assessments included the Morris Water Maze (MWM) test for memory and anxiety, as well as brain tissue analysis for biomarkers such as amyloid-β (Aβ), phosphorylated tau, and cytokines.
Study Findings
Global Usage Trends: Since its commercial release in 1974, glyphosate use has surged globally, with a 100-fold increase in application between the 1970s and 2016, making it the most widely used herbicide in agriculture.
The study’s first finding was that glyphosate exposure caused no changes in body weight but significantly increased mortality in 3xTg-AD mice, particularly during the recovery period. However, mortality was not dose-dependent, suggesting that underlying pathologies in 3xTg-AD mice may exacerbate the herbicide's effects. Behavioral tests revealed that glyphosate-exposed 3xTg-AD mice exhibited increased thigmotaxia, a marker of anxiety, during the MWM learning phase compared to NonTg controls.
Blood and brain tissue analyses showed that glyphosate and AMPA persisted in the brain cortex, with AMPA levels significantly higher in exposed groups. Additionally, brain weights were reduced in exposed mice, correlating with markers of neurodegeneration. Elevated concentrations of Aβ plaques and phosphorylated tau were observed in the hippocampus (Hp) and cortex (Ctx), highlighting glyphosate's potential to exacerbate AD progression.
Furthermore, both pro-inflammatory (e.g., TNF-α) and anti-inflammatory cytokines (e.g., IL-10) were elevated in exposed mice's brain and blood plasma, suggesting a prolonged and dysregulated neuroinflammatory response. These findings underscore the complex and lasting impacts of glyphosate on neuroimmune systems.
Conclusions
The present study provides novel evidence of glyphosate exposure exacerbating AD-like neuropathologies, including persistent inflammation, anxiety-like behavior, and neurodegeneration in mice. The research highlights AMPA accumulation in brain tissue even after an extended recovery period, emphasizing the herbicide's potential for long-lasting adverse effects.
"Our work contributes to the growing body of literature highlighting the brain's vulnerability to glyphosate exposure," the authors stated. "The persistence of biomarkers associated with neuroinflammation and AD-like pathologies warrants further investigation, particularly in light of glyphosate's widespread use."
While these results cannot be directly generalized to humans, they raise critical questions about glyphosate's potential impacts on mammalian neurodegenerative health. Further research is needed to assess its implications for rural populations, where exposure to this herbicide is common due to large-scale agricultural practices.
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