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Yale research finds way to restart brain cell growth

NEW HAVEN, Conn. - As some Yale students kill brain cells each weekend, Yale University researchers are working to grow them back.

A team led by Yale Medical School Neurobiology Chair Pasko Rakic has found a way to restart the growth of brain cells. The team's findings were published in the journal "Science" on Friday and have been heralded nationwide for their potential contribution to the treatment, or even prevention, of degenerative brain diseases like Alzheimer's.

Rakic's research team included graduate student Nenad Sestan and Spyros Artavanis-Tsakonas, a professor of cell biology at Harvard.

Although brain cells normally arrive at a fairly stable number by adulthood, the research team, experimenting on mice, was able to manipulate a kind of on-off switch that triggers cells' reproduction.

Known as "Notch signaling," the element that makes the process possible is the Notch receptor, which is present in neurons and the extensions they form during reproduction. The Notch receptor was first described in studies at Yale in the 1940s and then cloned at Yale in the 1980s. But the Notch receptor's role in regenerating adult brain cells had escaped identification until now.

Until adulthood, neurons grow by extending branches called dendrites and axons, which in turn make millions of connections.

What interests researchers is the increased activity of Notch signaling that accompanies the creation of the connections.

When the connections become stable, the brain establishes long-term memories that normally last throughout life.

In Alzheimer's patients, these stable connections start to disintegrate. Memories are lost. Patients move from forgetfulness to dementia and usually die five to 10 years after diagnosis.

The new study provides a clue to how the transition from growth to stability might occur.

Rakic said in a press release that his team has not only recognized the Notch receptor as part of the signal involved in the switch from growth to stability, but it has also identified the associated molecules that can turn the switch on and off.

Rakic and his colleagues found the role of the Notch receptor and these related molecules "new and unexpected."

The Notch signaling pathway gradually inhibits the making of these new connections, instead of stabilizing those that exist.

By inhibiting Notch activity in mature cells, the team was able to reverse this state of stability and renew neuron growth.

Scientists believe Notch signaling is involved in the progression of degenerative brain disorders like Alzheimer's, but the Yale team is still trying to determine what role Notch signaling plays in Alzheimer's Disease, Rakic said.

For example, researchers are uncertain whether Notch signaling prevents or accelerates the disease.

But by boosting understanding of the growth process of brain cells, the study's results could also open possibilities for treating and preventing other brain disorders that, like Alzheimer's, cause sufferers to lose memories and cognitive abilities.