"The effect of having lots of the human COX-2 protein is remarkable in these mice," says Andreasson. "At age seven months -- roughly similar to humans in their 20s and 30s -- they are fine, but as these mice get older they exhibit progressively greater memory deficits. These mice have real age-dependent memory loss, and higher age-dependent loss of brain cells that parallels the behavioral changes."
Because so much is already known about the human COX-2 protein, learning more about what it does in the brain, even the mouse brain, is a little easier, says Andreasson. "We already have tools to see where COX-2 is located in the brain and in individual nerve cells, and we can also test whether it's working by measuring levels of the molecules it makes."
COX-2 helps make a group of five molecules, called prostaglandins, that send signals to the nerve cell. Andreasson says one of the prostaglandins may be the real culprit behind COX-2's effects on memory and it's role in disease.
"If it's a prostaglandin, we can find out which is good and which is bad, and potentially target the bad one specifically to prevent memory loss or damage from aging or stroke or disease," she says. "The possibility would exist to prevent neurological problems and to do so with fewer side effects than blocking COX-2 itself."
While targeting prostaglandins is still hypothetical, current research is beginning to evaluate COX-2 inhibitors to prevent or delay neurological problems. For example, an ongoing study at Johns Hopkins and three other centers will determine whether using these drugs can affect development of Alzheimer's disease in older patients at high risk for it.
COX-2's role in exacerbating damage from strokes is another hot topic of pursuit among neurologists and neuroscientists. Another Hopkins presentation at the Society for Neu
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
14-Nov-2001