Brain cells in the cerebral cortex grow by extending neurites until they form connections with nearby cells. Illustrations A and B show how neurites will grow longer when they are in a low-density vs. high-density area. Illustration C offers a close-up view of how the cells connect to one another.

Yale scientists find way to restimulate brain cell growth

Yale scientists have discovered that the growth of brain cells, which normally ends in adolescence, can be re-stimulated in mature neurons with a molecular mechanism known as Notch signaling. Because Notch signaling also may be involved in the progression of degenerative diseases like Alzheimer's, the findings published in the Oct. 22 issue of Science could help scientists develop ways to treat, or even prevent, this and other brain disorders. "Our results not only help in our understanding of brain development, but they also have considerable implications for designing new treatments for many neurological disorders," says the study's principal investigator, Dr. Pasko Rakic, professor and chair of neurobiology at the School of Medicine. "One of the hallmarks of Alzheimer's disease is the alteration of brain cell processes that can lead to irreversible memory loss and cognitive abilities characteristic of the disorder," Rakic says. "While we are still trying to determine what role Notch signaling plays in Alzheimer's, the results of this study could open possibilities for treating and preventing these kinds of degenerative diseases." As the brain develops, neurons grow rapidly by extending neurites -- dendrites and axons -- which make millions of connections from birth up until adolescence, when the connections in the cerebral cortex begin to stabilize. As stabilization occurs, long-term memory is acquired, allowing people to remember things throughout their lives. This new study provides a clue to how the transition from growth to stability might occur. "We have identified the signaling pathway involved in the switch from growth to stability, as well as the associated molecules that can turn the switch on and off," says Rakic. The main element of the signaling pathway is the Notch receptor, which was first described in studies at Yale in the 1940s and was then cloned at Yale in the 1980s, but its role in adult brain cells has not been identified until now. In their study, Rakic and his colleagues found a new and unexpected role for the Notch gene and related molecules. The Notch receptors are present in neurons and their specialized processes called neurites. Neurons of the cerebral cortex -- a thin sheet of gray matter on the surface of the brain -- grow by extending their neurites and forming connections, both of which are accompanied by an increase in activity of the Notch signaling pathway. The Notch signaling pathway gradually inhibits the extension of neurites and keeps them stable in maturity. By inhibiting Notch activity in mature neurons, the team was able to reverse this state of stability and re-initiate neuron growth. These findings suggest that the Notch signaling pathway prevents neurites from forming new connections in the adult cerebral cortex, and therefore plays a role in regulation of growth and stability of neural connections. In Alzheimer's disease, a mutation of the gene presenilin is responsible for the early-onset of the disease. These new results provide a clue to how mutations in presenilin, which is known to affect Notch signaling, may contribute to alteration of neurites found in the disease. Rakic's research team included Yale graduate student Nenad Sestan and Spyros Artavanis-Tsakonas, professor of cell biology at Harvard. T H I SW E E K ' SS T O R I E S School of Music gets $10 million Yale scientists find way to restimulate brain cell growth Center's addition puts families and children at heart of Medical School Glamour lauds senior for commitment to public education Personalities overshadow issues in politics today, says journalist Divinity School honoring work of feminist theologian Letty Russell Students turn passion for education into teaching careers Retrospective exhibit showcases works of British Pop artist Exhibit of artists' rough drafts for masterpieces explores creative process Peabody exhibit pays tribute to pioneering scientist O.C. Marsh Architecture School highlights Daniel Libeskind's latest projects Study identifies common fears about genetic testing Grant to the Yale Cancer Center will support lymphoma research Yale singers' first production is a sampling of opera scene Divinity School event welcomes prospective students Pioneering biologist Clement L. Markert dies at age 82 Community can remember deceased loved ones at Evensong Service Workshops promoting collaborative research on women's health issues Search committee for dean of engineering . . . In the News . . . Campus Notes A Day of Dance: A Photo Essay Bulletin Home|Visiting on Campus| Calendar of Events|Bulletin Board Classified Ads|Search Archives|Production Schedule|Bulletin Staff Public Affairs Home|News Releases| E-Mail Us|Yale Home Page