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Needle-In-a-Haystack Search Identifies Molecule that Re-invigorates Brain Cell Production, Learning & Memory

  [ 29 votes ]   [ Discuss This Article ] • July 9, 2010

Researchers screened 1,000 molecules in live animal trials to find one that promotes & sustains hippocampal brain cells.

Free-wheeling biomedical researchers at the Dallas-based McKnight Lab (University of Texas Southwestern Medical School) are known for pursuing high risk projects likely to break new ground.

Now a team led by Professor Steven McKnight, PhD, has “found a compound that preserves newly created brain cells and boosts learning and memory in an animal study.” The study (“Discovery of a ProNeurogenic, Neuroprotective Chemical”) is an open access paper published in the July issue of Cell.

According to their news release…

Over a three-year period, a research team led by Dr. McKnight and Dr. Andrew Pieper, assistant professor of psychiatry and biochemistry at UT Southwestern, screened 1,000 individual molecules to see which ones might enhance the production of neurons in the adult mouse hippocampus - a region of the brain critical to learning and memory.

The scientists found that one of the compounds, called P7C3, achieved this by protecting newborn neurons from dying.

The researchers then administered P7C3 to “knockout” mice lacking a gene that controls the generation of new neurons in the hippocampus. Humans who lack this gene have a variety of learning disabilities, and the “knockout” rodents show related abnormalities as well as a poorly formed hippocampus.

When the “knockout” mouse received P7C3, however, normal structure and function of the hippocampus were restored.

In elderly rats, which characteristically show a decline in the birth and formation of hippocampal neurons, the researchers found that P7C3 increased both the birth and survival of new neurons, and the memory and learning capability of the aged rats.

“It’s been a wonderful experience,” Dr. Pieper said. “At first there was a lot of doubt, because we could have gone through the whole screen and found nothing.”

The researchers currently are studying the mechanism by which P7C3 protects cells from dying, and whether it might have any protective effect in other models of neurodegenerative disease. “We don’t know yet whether P7C3 can block the death of mature nerve cells, which is what occurs in humans with these conditions,” Dr. McKnight said.

Among the study’s supporting grants was the National Institutes of Health Director’s Pioneer Award, which is designed to allow researchers to pursue risky experiments that have the potential for producing highly innovative results. “When I received the award, I thought ‘I’m not going to waste it on something safe - I’m going to go for it.’ That’s what the NIH expected of me and my team,” Dr. McKnight said.

“I’d like to give the NIH credit for betting on ‘cowboy’ science. If this pans out, it will be the most useful contribution of my career.”

Source: University of Texas Southwestern Medical Center news release, July 8, 2010

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