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The Fate of Brain Cells
by Paul Muhlrad
A fountain of youth springs from within the brain of every mammal, report HHMI investigator Alexandra L. Joyner and her former postdoctoral associate Sohyun Ahn in the October 6, 2005, issue of Nature. No, the two researchers haven't unlocked the secret to immortality. But their discovery of a method to visualize an elusive population of stem cells that has the potential to regenerate nerves and other brain cells may explain how certain regions of the brain rejuvenate themselves. Moreover, the findings may allow researchers to tap the revitalizing powers of stem cells for repairing injured and diseased brain tissue.
Two regions of the mouse brain—the hippocampus, which controls short-term memory, and the olfactory bulb, which processes odors—contain neurons that are continually replenished throughout adult life. Some neurobiologists have thought that these fresh brain cells arise from a population of rapidly dividing but short-lived stem cells called transient amplifying cells, but others have proposed that these cells must derive from infrequently dividing "quiescent neural stem cells" lurking within the brain. Indirect evidence has hinted that such quiescent cells do exist, but, until now, says Joyner, no one had effectively pinpointed the cells in living brains.
Ahn and Joyner, working at New York University's Skirball Institute of Biomolecular Medicine, devised a method to mark all stem cells and their descendants in the brains of live laboratory mice over the animals' lifetimes. After marking the stem cells, the researchers administered a drug called AraC, which efficiently kills only rapidly dividing brain cells. "We killed off the transient amplifying cells and then showed that there is another population of cells still capable of replenishing," Joyner explains. "And then we did it a year later. We killed off the transient amplifying cells again, and the cells we had marked the year earlier could still replenish," proving the existence of long-lived quiescent stem cells in living animals.
Because the normal life span of a mouse is only about 1 year, the results imply that the quiescent stem cells survive throughout the life of the animal. "The idea in humans is that they would lie mostly dormant for 80 years," says Joyner.
Now she wants to learn how to harness the cells for regenerating new tissue types. "If we could infuse the right type of growth factors into the brain after injury or disease, perhaps we could mobilize them to do more than what they normally do."
Some other potential applications may involve selective destruction rather than harnessing, as Joyner says that similar stem cells elsewhere in the body may be involved in spreading cancer. "There's this idea that there are stem cells in cancers, the ones that allow aggressive tumors to escape therapies. There may be quiescent stem cells in cancers, which produce the rapidly dividing cells that eventually are lethal."