It has been found in previous studies that the HIV-1 coat protein GP120 can stimulate monocytes to produce substances which are toxic to neurons. This toxicity is intimately involved with calcium metabolism in general and the NMDA receptor in particular. Utilizing primary cultures of both rat and human neurons for in vitro studies, several techniques, including high resolution NMR spectroscopy, will be utilized to understand these different processes. We have performed experiments on the 600 MHz system at the FBML on a variety of samples that examined directly the effects of the HIV virus on monocytes and on brains of transgenic (SCID) mice inoculated directly with HIV infected monocytes. Significantly, we have found that monocytes infected with HIV contain a higher concentration of glutan-iine and glutamate, the latter known to cause excitotoxic injury to neurons.
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