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Mice with COX-2 Protein Exhibit Memory Loss Similar to Alzheimer’s Disease

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A new study shows mice engineered to make the human COX-2 protein, develop memory problems and mimic symptoms found in Alzheimer’s disease. This is according to a recent presentation by scientists from the Johns Hopkins School of Medicine, and the biomedical research company Pharmacia at the annual meeting of the Society for Neuroscience.

“The really exciting thing is that this protein is turning out to be involved in so many things, and we already have the means to target it, to block it,” says Katrin Andreasson, M.D., assistant professor of neurology and neuroscience at Johns Hopkins. “It makes it very conceivable that in the years to come we could prevent these diseases.”

Drugs that reduce swelling, like ibuprofen and newer anti-inflammatories like Celebrex and Vioxx, work by blocking COX-2. However, Andreasson cautions that a lot of work remains in order to learn whether these drugs might prevent neurological disease or damage in people.

The researchers measured the animals’ abilities to learn and remember using a variety of tests, including mazes and swimming tests. The animals’ behaviors in the test situations reflected how brain levels of the human COX-2 protein affected their learning and memory at different ages. The more COX-2 protein the mice make in their brains, the more pronounced the memory problems became, and the faster those problems developed.

“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.”

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