January 30, 2004

Stem Cell Regulator Could Hold Key to Staving Off Age-related Brain Changes

Salk News

Stem Cell Regulator Could Hold Key to Staving Off Age-related Brain Changes

La Jolla, CA – A brain-specific genetic switch protein known as a receptor has been found to control the fate of adult stem cells in the brain, according to a Salk Institute study.

The findings, published in the Jan. 1 issue of Nature, suggest a way to prevent the learning and memory declines that occur during the aging process, as well as possible ways to treat neurodegenerative diseases and brain injury. The research also shows for the first time how adult brain stem cells begin their transformation into specialized cells.

Professors Ronald Evans and Fred H. Gage and their colleagues discovered that the receptor, called TLX, is needed to maintain proliferating stem cells in the brains of adult mice. Defects in the activity of TLX in mice result in violent and aggressive behavior that is often seen in neurodegenerative diseases and brain injury. Most important, re-introducing normal TLX into cells derived from mice with defective TLX restored their ability to behave as adult neural stem cells.

“TLX is present in the developing brain, but isn’t essential for early development,” said Gage. “It is surprisingly crucial for the function of adult nerve cells. Since this function declines with age, especially in areas of the brain important for learning and memory, TLX may be a target for protecting against age-related changes associated with cognitive decline.”

The researchers found that stem cells that have the TLX receptor could proliferate and differentiate into any of the variety of cells found in the adult brain. But without the receptor, none of the cells could grow, resulting in dramatic behavioral changes in the mice. These changes were reversed and cells were again able to proliferate when the scientists reintroduced TLX.

Gage is known for his earlier finding that the brain can regenerate nerve cells in adulthood, which lead to the discovery of adult stem cells in the brain. Since that discovery, researchers have been trying to find out exactly how the stem cells develop into working parts of the nervous system.

“If we can learn how to control the switch we might be able to stimulate the formation of new brain cells and restore or preserve learning and memory. With this switch in hand we will begin looking for drugs that might regulate its activity to stimulate brain function,” said Evans.

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. Jonas Salk, M.D., founded the institute in 1960 with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

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