Soldiers in war zones and farmers tending their fields can have in common chronic exposure to chemicals that impact their nerves.
In large doses these agents, called organophosphates, are proven, rapid killers of people and pests that can also produce chronic disabilities such as problems with learning and memory, headaches and pain, said Dr. Alvin V. Terry Jr., pharmacologist at the Medical College of Georgia at Georgia Health Sciences University.
A Department of Defense grant is helping him document the less understood - and probably more common - consquences of low-dose exposure for long periods.
"The use of these chemicals is like making the Faustian bargain," said Terry. "They are great for enhancing farming productivity and getting rid of vector-born illnesses like malaria and yellow fever, but they are almost ubiquitious in our environment." Conceding the last thing he wants is to encourage elimination of useful agents, he hopes instead that a prospective look at their cumulative toll will help identify ways to stop the ill effects.
"Once we have identified there is a problem and we know the mechanism, we have a much better chance of treating people," he said. Terry will be looking at varying doses of chlorpyrifos, an insecticide used by farmers and the military during the Gulf War, as well as the nerve agent, diisopropylfluorophosphate.
He is the first to look at the agents' impact on the axons, which enable brain cells to communicate.
"We are talking about the highway," he said of the pathway that has information, molecules, growth factors and other things made by the cells moving constantly in both directions. Terry is finding this fundamental brain function may be a particular target of chronic exposure to organophosphates. He's already shown animals with chronic exposure have impared communication in the body.
Now he's looking in the brain at axons as well as the white matter, which surrounds and helps insulate the nerve fibers to ensure clear communication. Brain studies have documented a shrinkage of white matter in some Gulf War veterans; Terry want to see if chronic exposure has a similar impact: enough to hamper but not destroy communication. He was corresponding author on a paper published earlier this year in the journal Neurotoxicology and Teratology that indicates chronic, low-level exposure leads to chronic spatial learning and memory deficits.
Dr. Nathan Yanasak, Director of GHSU's Core Imaging Facility for Small Animals, is collaborating on the new study that will do baseline then follow-up brain images of rats after low-level exposure for 30 days. Then researchers will follow the rats until the agents are no longer detectable in the body. A manganese tracer will gauge activity up and down axons.