There is general consensus that the altered behavior associated with HIV infection, referred to as AIDS dementia, is a result of a chronic infection of central nervous system monocyte/macrophages. While one end product of HIV infection in the brain is neuronal death, there is increasing data to suggest that the increased presence of monocyte/macrophages and their toxic products may correlate with dementia. The investigators hypothesize that there is a subset of """"""""activated"""""""" peripheral HIV-infected monocytes that produce toxic factors and this subset is increased in dementia. These """"""""activated"""""""" monocytes enter the brain and produce a chronic nonlytic infection signaling an apoptotic loss of neural cells. This application will study monocyte subsets from patients with AIDS dementia including their toxic effects on human neural cells in vitro.
The specific aims are: 1) to identify and characterize monocyte subsets from patients with AIDS dementia; 2) to determine in a longitudinal study if a monocyte subset predicts development of clinical dementia; 3) to determine if the soluble factors produced from this subset cause neural cell apoptosis; 4) to determine the temporal level of gene modulation in the presence of monocyte factors; and 5) to determine how neurotoxicity can be reversed.
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| Pulliam, L; Irwin, I; Kusdra, L et al. (2001) CPI-1189 attenuates effects of suspected neurotoxins associated with AIDS dementia: a possible role for ERK activation. Brain Res 893:95-103 |
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