Gulf War Illness

One morning at SfN, a friend and I were looking over the day's schedule deciding which posters we were going to see. We glanced by one abstract containing the words 'Gulf War Syndrome' and 'mouse'. We were a bit amused at first, trying to figure out exactly how one goes about making a mouse line that has Gulf War Syndrome. Does Harlan raise them in a war zone?

Of course that's not the case. Instead, rats or mice are exposed to various chemicals that were potentially used in the Persian Gulf War in the early 1990s. These include pesticides and nerve gases, many of which are acetylcholinesterase inhibitors that prevent the break-down of excess acetylcholine at synapses in the CNS and PNS.

Gulf War Illness affects many soldiers who served in Operation Desert Storm and/or Desert Shield; some reports estimate this number to be as high as 25% to 30% of veterans! Symptoms of Gulf War Illness presented slowly and, in some cases, took almost two years. Another confounding factor is the seemingly random set of symptoms, which include depression, bronchitis, stomach upset, chronic fatigue, memory problems, and musculoskeletal issues.

Effort is now being put forth by the US Department of Veterans Affairs to study this illness, and several of these research studies were presented at SfN.

Many veterans report problems related to memory recall. Because the hippocampus plays a major role in learning and memory, one study conducted by HE Speed et al. from UT Southwestern investigates the effect of chlorpyrifos, a common insecticide used during the Gulf War, on this brain structure. They found that chlorpyrifos exerts a biphasic effect on synaptic transmission. Closely following initial exposure, mice actually showed an enhancement in synaptic transmission and a small increase in learning and memory. However, the later phase was characterized by a 50% decrease in synaptic transmission, which indicates a loss in synaptic efficacy, in the number of synapses, and/or in the number of neurons. It's interesting to note that this later effect was detected three months after exposure to chlorpyrifos, consistent with the delayed onset of symptoms associated with Gulf War Illness.

Another study by VK Parihar et al. once again looked at the hippocampus and the effect of chemicals and stress on neurogenesis within this brain structure. The group found that rats exposed to pesticides and stress experienced a significant reduction in hippocampal neurogenesis, which may underlie some of the memory and mood disruptions reported by veterans of the first Gulf War.

Finally, P Ferchimin et al. are investigating the possibility that a compound found in the leaves and flowers of tobacco plants (4R) can impart neuroprotection following exposure to insecticides or nerve toxins. Tested on acute hippocampal slices, the researchers found that treatment with 4R 30 minutes after exposure to a toxin prevented any loss of neurons. If 4R was applied 1 hour after exposure, only 30% of the neuronal population was lost. Neuron survival was determined via electrophysiological recordings of a 'pop spike', which is an extracellular measurement of neurotransmitter release from a population of neurons.