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Agent Orange, a herbicide used during the Vietnam War, is a well-known poison with widespread health effects. Although Agent Orange has not been used for decades, there is growing interest in its effects on the mental health of aging veterans. A new study by Brown University scientists shows how Agent Orange affects the brain and how this process can lead to neurodegenerative diseases.

Research shows that exposure to Agent Orange herbicide chemicals causes frontal lobe brain tissue damage in laboratory mice that resembles the molecular and biochemical abnormalities seen in the early stages of Alzheimer’s disease. A preliminary online version of the paper detailing the findings was published Feb. 13 and is scheduled for publication in the Journal of Alzheimer’s Disease.

Study author Dr. Suzanne M. De La Monte, a Brown University physician-scientist, said the findings could have important implications for military veterans who were exposed to Agent Orange during the Vietnam War.

“If we can show that early exposure to Agent Orange leads to later neurodegenerative disease, that gives veterans an opportunity to get help,” De La Monte said.

But the findings of this study have much more significance, he added, because the toxins found in agent oranges are also present in lawn fertilizers.

“These chemicals don’t just affect veterans; they affect our entire population,” said De La Monte, professor of pathology and laboratory medicine and neurosurgery at Brown’s Warren Alpert Medical School.

Agent Orange is a synthetic herbicide that was widely used between 1965 and 1970 during the Vietnam War. Members of the US military were exposed to the chemical when they were stationed near enemy territory that had been sprayed by aircraft. Government reports showed that exposure to Agent Orange also caused birth defects and developmental disabilities in children born to Vietnamese women living in affected areas. Over time, studies have shown that exposure to Agent Orange was linked to an increased risk of certain cancers, as well as heart disease and diabetes.

Research also revealed an association between exposure to Agent Orange and the later development of neurodegenerative diseases, and significantly higher rates and earlier onset of dementia. However, in the absence of a proven causal link between Agent Orange and diseases associated with aging, studies are needed that improve understanding of the mechanisms by which the herbicide affects the brain.

“Scientists felt that Agent Orange was a neurotoxin with potential long-term effects, but they had not been clearly demonstrated,” De La Monte said. “That’s what we were able to show with this study.”

The analysis was conducted by De La Monte and Dr. Ming Tong, a research associate in medicine at Brown. Both are also affiliated with Rhode Island Hospital, which is affiliated with the Warren Alpert Medical School. His research builds on his recent studies of exposure to Agent Orange chemicals on immature human cells from the central nervous system, which showed that short-term exposure to Agent Orange has neurotoxic and early degenerative effects related to Alzheimer’s. .

Researchers investigated the effects of two main components of Agent Orange (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) on markers of Alzheimer’s neurodegeneration using samples from the frontal lobes of laboratory mice. Adult, intact brain tissue samples contained a whole complex array of cell types and tissue structures.

The scientists treated the samples for total exposure to Agent Orange as well as its individual chemical components, and observed underlying mechanisms and molecular changes.

They found that treatment with Agent Orange and its components caused molecular and biochemical abnormalities in brain tissue consistent with brain cell degeneration and cytotoxic injury, DNA damage, and other problems.

The approach used by the researchers helped better define the neuropathological, neurotoxic and neurodegenerative consequences of exposure to Agent Orange toxin in young, otherwise healthy brains, such as Vietnam War-era military personnel and many in Vietnam. would have been for local residents.

“Finding early effects tells us that there is a problem that will cause problems later and also gives us a handle on the mechanism by which the agent is causing the problem,” said de la Monte. said LaMonte. “So if you were going to intervene, you’d know to focus on that initial effect, monitor it and try to reverse it.”

Del La Monte hopes to engage in additional research on human brain tissue to examine the long-term effects of Agent Orange exposures on aging and progressive neurodegeneration in Vietnam War veterans.

The US government banned the use of Agent Orange in 1971. However, de la Monte said the chemicals persist in the environment for decades. The widespread, uncontrolled use of Agent Orange in herbicides and pesticides is such that one in three Americans has biomarker evidence of prior exposure, according to the study’s authors.

Despite growing recognition of 2,4-dichlorophenoxyacetic acid’s widespread toxic and carcinogenic effects, researchers note that concern has not reached a high enough level for federal agencies to ban its use. The researchers concluded that the results of this study and another recent publication support the notion that Agent Orange, along with its independent components (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) in adults It has dangerous negative effects on the brain. and the central nervous system.

That’s why it’s so important to look at the effects of these chemicals, De La Monte said. “They’re in the water; they’re everywhere. We’re all exposed.”

This research was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (R01AA011431, R01AA028408).

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