Agent Orange, a herbicide used during the Vietnam War, is a known toxin with broad health effects. Although Agent Orange has not been used for decades, there is growing interest in its effects on the brain health of elderly veterans. A new study by scientists at Brown University reveals the mechanisms by which Agent Orange affects the brain and how those processes can lead to neurodegenerative diseases.
Research shows that exposure to the herbicidal chemicals in Agent Orange damages the frontal lobe brain tissue of laboratory rats with molecular and biochemical abnormalities similar to those found in early-stage Alzheimer's disease. An early version of this article detailing the findings was published online on February 13 and is scheduled for publication in the Journal of Alzheimer's Disease.
The findings could have important implications for military veterans who were exposed to Agent Orange during the Vietnam War, said study author Dr. Suzanne M. De La Monte, a physician and scientist at Brown University.
“If we can show that prior exposure to Agent Orange leads to subsequent neurodegenerative disease, that will give veterans a chance to get help,” De La Monte said.
But the study's findings have much broader significance, he added, because Agent Orange toxins 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 defoliant 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 show that Agent Orange exposure also caused birth defects and developmental disabilities in babies born to Vietnamese women residing in the affected areas. Over time, studies showed that Agent Orange exposure was associated with an increased risk of some types of cancer, as well as cardiovascular disease and diabetes.
The research also revealed associations between Agent Orange exposure and the subsequent development of degenerative diseases of the nervous system, 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 to improve understanding of the process by which the herbicide affects the brain.
“Scientists realized that Agent Orange was a neurotoxin with potential long-term effects, but they were not 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 associated with Rhode Island Hospital, an affiliate of the Warren Alpert School of Medicine. His research is based on his recent studies of exposure to Agent Orange chemicals in immature human cells of the central nervous system, demonstrating that short-term exposure to Agent Orange has early neurotoxic and degenerative effects related to Alzheimer's.
The researchers investigated the effects of the 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 rats. The mature, intact brain tissue samples included a full and complex range of cell types and tissue structures.
The scientists treated the samples with cumulative exposure to Agent Orange, as well as its separate chemical components, and observed the underlying mechanisms and molecular changes.
They found that treatment with Agent Orange and its components caused changes in brain tissue corresponding to degeneration of brain cells and molecular and biochemical abnormalities indicative of cytotoxic injury, DNA damage and other problems.
The approach used by the researchers helped them better characterize the neuropathological, neurotoxic, and neurodegenerative consequences of Agent Orange toxin exposure in young, otherwise healthy brains, as would have been the case in War-era military personnel. of Vietnam and many local residents in Vietnam.
“Looking for early effects tells us that there is a problem that is going to cause problems later and also gives us insight into the mechanism by which the agent is causing problems,” De La Monte said. “So if you were going to intervene, you would know to focus on that early effect, monitor it, and try to reverse it.”
Del La Monte hopes to engage in additional research on human brain tissue to evaluate the long-term effects of Agent Orange exposure in relation to aging and progressive neurodegeneration in Vietnam War veterans.
The use of Agent Orange was banned by the United States government in 1971. However, the chemicals remain in the environment for decades, De La Monte said. According to the study authors, the widespread and uncontrolled use of Agent Orange in herbicide and pesticide products is such that one in three Americans has biomarker evidence of prior exposure.
Despite growing recognition of the widespread toxic and carcinogenic effects of 2,4-dichlorophenoxyacetic acid, researchers noted that concern has not reached a sufficient level for federal agencies to ban its use. The researchers conclude that the results of this study and another recent publication support the idea that Agent Orange, as well as its independent constituents (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) exert alarming adverse effects on the mature brain. and 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've all been exposed.”
This research was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (R01AA011431, R01AA028408).