University of Texas (UT) Southwestern Medical Center researchers have found a compound that preserves newly created brain cells and boosts learning and memory in an animal study.
The study of this compound springs from a $2.5 million National Institutes of Health (NIH) Director’s Pioneer Award to Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and senior author of the study.
Over a 3-year period, the 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.
Dr. McKnight was one of the first 12 recipients of the NIH 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.”
Dr. Francis Collins, director of the NIH, said Dr. McKnight’s results exactly fit the award’s purpose.
“The NIH Director’s Pioneer Award gives highly innovative investigators the freedom to pursue bold new avenues of research. Such approaches can yield substantial payoffs, as in the case of the exciting clinical implications of Professor McKnight’s basic neurobiological research discovery,” Dr. Collins said.
Illustration: Drs. Joseph Ready (from left), Jef De Brabander, Andrew Pieper, and Steven McKnight discovered a compound that boosts learning and memory in rodents.
University of Texas Southwestern News Release (07/08/10)
Abstract (Cell; Vol. 142, Issue 1, 39-51 (07/09/10))