Neurotoxicity From Chronic Exposure to Depleted Uranium
Annual rept. 1 Apr 2003-31 Mar 2004
CHICAGO UNIV IL
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This project is designed to test the hypothesis that chronic exposure to depleted uranium DU impairs neuronal processes underlying cognitive function via alterations induced at hippocampal glutamatergic synapses. As prescribed by the Statement of Work, efforts in year 2 concerned completion of Technical Objective I establishment of chronic exposure protocol and achieving substantial progress on Technical Objective 2 defining integrity of hippocampal glutamate release. Blood and brain concentrations of uranium U increased monotonically as a function of exposure level and duration up to 12 months, and were correlated with a decrease in rate of growth. Acute exposure to U in vitro diminished K-stimulated glutamate and GABA release in a concentration-dependent fashion in hippocampal synaptosomes. The inhibitory effect on evoked glutamate release was more potent IC50 2.61 micron M than that on GABA IC50 204 micron M, and was similar to IC50 values for transmitter release exhibited by other multivalent metal ions. Studies are currently underway examining the effects of chronic exposure on transmitter release in vivo. Given the similarity of effects of U on transmitter release to those of other multivalent metals and the fact that exposure in military scenarios is continuing, additional studies are warranted on uranium actions in several experimental settings.
- Anatomy and Physiology
- Medicine and Medical Research