A NEW MODEL FOR GULF WAR SYNDROME: CHLORPYRIFOS AFFECTS LOCUS COERULEUS FIRING
Contact: Donald C Cooper
Researchers at the University of Colorado, Boulder have made an important step in Understanding Gulf
Neuroscientist Donald Cooper, Ph.D. and his team found that a common organophosphate insecticide used in the Gulf War was capable of changing neuronal activity in a rodent brain region, known as the Locus Coeruleus, a brain region that is critical for attention, anxiety, and addiction.
Their paper, released in Nature Precedings, is the first report describing how exposure to the toxic metabolite of the insecticide, chlorpyrifos leads to lasting changes in neuronal activity that persist long after exposure.
These researchers have previously shown similar changes in neuronal signaling to be similar to those that follow withdrawal from heroin and morphine and would likely produce similar states of anxiety, discomfort and memory problems.
The paper is available in Nature Precedings and was funded, in part, by the University of Texas, Southwestern Medical center and the University of Colorado, Boulder.
Gulf War Syndrome: A role for organophosphate induced plasticity of locus coeruleus neuron
Jun-li Cao, Andrew L. Varnell & Donald C. Cooper
Gulf War syndrome is a chronic multi-symptom illness that has affected about a quarter of the deployed veterans of the 1991 Gulf War. Exposure to prolonged low-level organophosphate insecticides and other toxic chemicals is now thought to be responsible. Chlorpyrifos was one commonly used insecticide. The metabolite of chlorpyrifos, chlorpyrifos oxon, is a potent irreversible inhibitor of acetylcholinesterase, much like the nerve agent Sarin.
To date, the target brain region(s) most susceptible to the neuroactive effects of chlorpyrifosoxon have yet to be identified. To address this we tested ability of chlorpyrifos oxon to influence neuronal excitability and induce lasting changes in the locus coeruleus, a brain region implicated in anxiety, substance use, attention and emotional response to stress. Here we used an ex vivo rodent model to identify a dramatic effect of chlorpyrifos oxon on locus coeruleus noradrenergic neuronal activity.
Prolonged exposure to chlorpyrifos oxon caused acute inhibition and a lasting rebound excitatory state expressed after days of exposure and subsequent withdrawal.
Our findings indicate that the locus coeruleus is a brain region vulnerable to chlorpyrifos oxoninduced neuroplastic changes possibly leading to the neurological symptoms affecting veterans of the Gulf War.