Atrazine exposure ages certain brain cells in mice so they stop dividing and growing.

Exposure to a widely used herbicide called atrazine (AT) can make nerve cells age faster and harm the hypothalamus, an essential part of the brain, increasing the risk of neurodegenerative disease, according to a recently released study in mice. 

A complete nerve cell (neuron) structure and sufficient mature nerve cells are critical for the central nervous system to work properly. The study, published this month [Dec. 13, 2024] in Research, shows the number of nerve cells and mature nerve cells in the mouse brain “significantly decreased” after exposure to atrazine. 

“These results directly proved the neurotoxicity of AT,” the researchers say.

Atrazine is a common surface water/drinking water pollutant and endocrine disruptor that poses environmental and health risks. It has been linked to reproductive complications, including fetal development problems and birth defects, and certain cancers in humans. Atrazine has also been associated with liver, kidney, and heart damage in animals, according to the CDC.

The new study shows that atrazine exposure ages certain brain cells in mice, causing them to stop dividing and growing. It also highlights for the first time the role of a specific stress response pathway in disrupting the processes healthy cells use to detect, repair or remove damaged parts.  

In addition, the study reveals how atrazine exposure can seriously damage the hypothalamus, which is important for controlling hormones and helps regulate the body’s stress response, growth, metabolism, and reproduction. Most research on the hypothalamus has focused on how atrazine affects hormones—and not how it damages the structure and shape of the hypothalamus, the researchers say.

The research comes as the EPA considers a proposal to raise the acceptable level of atrazine in watersheds from an average of 3.4 micrograms per liter to nearly three times as much.  

The study’s findings show that atrazine in mice:

• Damages nerve cells (neurons) and activates microglia, immune cells in the brain that act as its “first responders” to injury, infection, or disease
• Sends certain brain stem cells (Hypothalamic Neural Stem Cells, or HtNSCs) to the areas of injury in the hypothalamus
• Overly activates the body’s stress response system (Integrated Stress Response pathway, or ISR), which makes these HtNSCs age prematurely (stop dividing and growing) and impairs their ability to maintain and repair the hypothalamus by multiplying and turning into other types of nerve cells

In other words, even though the mouse brain tried to repair damage to the hypothalamus by recruiting stem cells, these cells wound up being “aged” and ineffective at healing.  

Growing evidence suggests that persistent exposure to pesticides such as atrazine is linked to the prevalence of age-related neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.

“Importantly, our findings provide preliminary evidence of a potential association between AT contamination and the development of aging-related NDs, which may help raise public health awareness regarding AT contamination,” the researchers say.

Mixed policies, despite data linking atrazine to health risks

People are typically exposed through contaminated soil, groundwater or drinking water to atrazine, which is the second-most commonly used weed killer globally after glyphosate with an annual usage of 180 million pounds (90,000 tons). 

In the U.S., more than 70 million pounds (35,000 tons) of atrazine are applied by certified workers, most often on farms and along highways and railroads.

The European Union banned atrazine in 2004 after it was found to regularly exceed the maximum limits in groundwater. In 2020, the EPA banned atrazine use in Hawaii and some U.S. territories, including Puerto Rico and Guam.

A previous study by these same researchers showed that mice exhibited spatial learning and memory impairments after atrazine exposure. In this study, they gave mice different doses of atrazine and studied its effects on HtNSCs and brain damage. They also looked into how atrazine causes HtNSC aging by analyzing gene activity and tested the findings in lab-grown brain cells.

The researchers say atrazine-induced damage to the hypothalamus includes the breakdown of cell nuclei (which contain DNA) and the protective covering of nerve cells (myelin sheath). Atrazine also degrades important cell structures like mitochondria, which produce most of a cell’s energy and can trigger cell death (apoptosis) when a cell is damaged beyond repair.

The research team also found in nerve cells more lipofuscin, a pigmented substance that is a sign of cell aging and can interfere with the cell’s ability to work as well as it should.

Additional experiments with another neural stem cell line confirmed the findings, the study shows. Those cells also showed signs of aging, DNA damage, and losing their ability to grow and form new neurons when exposed to atrazine.

The team did not test lower doses of atrazine or investigate its effects at more environmentally realistic levels, which they say limits how closely these results can be linked to real-world exposure. They also focused on how atrazine affects stem cells in the hypothalamus but did not fully explore how exposure might impact the entire nervous system.

Reference

Chen J, Dai X-Y, Malhi KK, et al. A new insight into the mechanism of atrazine-induced neurotoxicity: Triggering neural stem cell senescence by activating the Integrated Stress Response Pathway. Research. 2024;7. doi:10.34133/research.0547