AIDS interferes with stem cells in...(s acting by inhibiting stem cell prolife...)

Date:8/15/2007

s acting by inhibiting stem cell proliferation. Next, they confirmed these results in a special mouse strain bred to express HIV/gp120 in its brain. This mouse model for AIDS dementia mimics several features of the disease process found in humans. They observed a significant decrease in the number of proliferating stem cells in the brains of HIV/gp120-mice compared with similar tissue from normal, wild-type mice.

HIV/gp120 is known to interact with two receptors, called chemokine receptors, which are expressed on aNPCs. The researchers discovered that the same two receptors were targeted by HIV/gp120 sourced from either mouse or human brain tissue.

In search of a mechanism behind the finding that HIV/gp120 reduced proliferation of aNPCs, the scientists studied the effect of the protein on the cell cycle. Cells undergo seasons or cycles, known as G1, S, G2, and M (for mitosis, or cell division). They found that cells exposed to HIV/gp120 got stuck in the G1 or resting phase, and that the cell cycle was arrested.

Cell cycle is studied intensively by cancer researchers who have delineated certain checkpoint pathways that can jam cell proliferation, one of the key behaviors of cancer. Checkpoint pathways are overcome by cancers when they fool the bodys normal machinery into producing more cancerous cells. With dementia, it turns out that the opposite is true: the Burnham team discovered that HIV/AIDS could co-opt the checkpoint pathway to prevent stem cells in the brain from dividing and multiplying.

One such checkpoint pathway is modulated by an enzyme called p38 mitogen-activated protein kinase (MAPK), whose activity is known to disrupt the cell cycle. In mature nerve cells, the Burnham team had previously shown that HIV/gp120 activates the p38 MAPK pathway to contribute to cell death. Lipton and colleagues now report that the p38 MAPK pathway is also the mechanism underlying decreased stem cell proliferation in the brain associated with H
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Contact: Nancy Beddingfield nbeddingfield@burnham.org 858-646-3146 Burnham Institute Source:Eurekalert

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