Fertilizing Future Brain Cells

By Tina Hesman Saey, Science News

Wait until the Miracle-Gro people hear about this.

Researchers have discovered a new chemical compound that helps newborn neurons grow into mature brain cells. In mice, the chemical helped baby neurons survive a particularly tough adolescence in which 60 to 70 percent of the cells typically die, researchers report in the July 9 Cell.

The scientists tested 1,000 chemicals for the ability to stimulate neurogenesis — the development of neurons from birth to fully functional brain cells — in the brains of mice. The team, led by Andrew Pieper and Steven McKnight of the University of Texas Southwestern Medical Center at Dallas, found eight compounds that could make neurons grow. Computer analysis further narrowed the field to just one compound, dubbed P7C3, with the right properties that make it attractive as a candidate for drug development.

P7C3 doesn’t cause more neurons to be born, but it does help protect newborn neurons as they grow and wire themselves into the brain’s hippocampus, an important learning and memory center.

In additional experiments, old rats given daily injections of the chemical retained the ability to learn and remember the location of a submerged platform better than rats given placebo shots, the researchers found. And the old rats receiving P7C3 didn’t lose as much weight and become as frail as their counterparts did. 

These results suggest that P7C3, or chemicals like it, might one day be useful in staving off neurodegenerative diseases, such as Alzheimer’s, or protecting memory and learning abilities from the ravages of aging. “If you preserve neurogenesis in the hippocampus of an older person, I think that would be good for them,” McKnight says. But much research still needs to be done before the chemical could be tested on people, he says.

For instance, the researchers don’t know exactly how P7C3 works. Tests show that the compound helps cellular power plants called mitochondria stay healthy. Unhealthy mitochondria are known to send a distress signal that triggers a form of cell suicide known as apoptosis. But what the chemical does to keep mitochondria happy, and thus help neurons live longer, is still a mystery. 

Whether P7C3 can protect already mature brain cells from damage and death is also unknown.

The research team’s approach to finding a neurogenesis-stimulating compound is unusual, says Huda Zoghbi, a neurobiologist and Howard Hughes Medical Institute investigator at Baylor College of Medicine in Houston. When doing such large chemical screens, “most people do things in a [lab] dish,” she says. But Pieper and McKnight tested the chemicals in living animals. “This one really does it the hard way,” Zoghbi says.

Although it takes more work to test hundreds of chemicals in animals instead of on cells in a lab dish, the results may be more relevant. Often chemicals that show promise in the dish fail when tested on whole animals.

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