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New Neurons Work in an Old Brain

By Mark K. Anderson

Until recently, prevailing scientific wisdom held that the human brain is closer to a game of hearts than one of gin rummy. As a young adult, your skull contains all the brain cells you'll ever have. No new cards are dealt, and from there on in, all that can be done is discard.

Yet, since the late 1990s, a spate of scientific research has begun to establish that adults do generate new brain cells in some regions of the brain, well into old age.

And now, for the first time, scientists have seen that new neurons become functional members of the brain, forging new connections and firing "action potentials" like any other neuron.

Although this latest discovery has only been observed in the brains of mice, the analogy to humans suggests that the rules of the card game have indeed changed. It also points toward new directions in potential therapies for neurological disorders or brain injuries.

"What we have going on here is a periodic insertion of a new, young brain cell within the context of the older cells in the environment," said Fred Gage of the Salk Institute for Biological Sciences. "This gives a self-renewal property to the structure, by adding these new more malleable cells."

Gage is one of six authors of a letter that appears in Thursday's edition of Nature. The letter demonstrates that new brain cells (neurons) in adult mammals quickly become fully functioning components of the neural network. These neurons were observed as far back as 1962 by Joseph Altman of MIT.

This process, called "neurogenesis," has been observed in the hippocampus and olfactory bulb regions of the brain. The former is responsible for aggregating and processing memories -- although not for storing them. The latter, as the name suggests, deals with the sense of smell.

Gage et al. studied a region of the hippocampus in adult mice. His team used a special breed of retrovirus that makes the cells it has infected appear fluorescent green. Thus, since this retrovirus only attaches itself to neurons undergoing cell division, they had effectively pioneered a simple color-coding scheme for finding new neurons: Pre-existing neurons (which do not divide) appeared normal; fledgling neurons (which do) stood out like they'd been marked with a highlighter pen.

"We could see them," he said. "They had branches, they had axons, they had dendrites. They were complex. They looked reasonably like their neighbors, which were not labeled (with the retrovirus)."

This work provides a "definitive proof" of neurogenesis in the hippocampus, said Pasko Rakic, of Yale Medical School's neurobiology department. In a feature article earlier this year, The New Yorker called Rakic "perhaps the foremost student of the primate brain in America." His longstanding skepticism about neurogenesis has led him to be stereotyped as the "read my lips -- no new neurons" guy, as he told the magazine.

Yet Rakic is impressed by Gage's new findings. He sees a potential for neurogenesis therapies that could patch up some types of brain damage or disease.

"Since this is not yet healing any disease, this is just a model system," he said. "But if you could incorporate these new cells into the spinal cord, for example, you could cure diseases that affect dying cells in the spinal cord."

Even if neurogenesis cannot be taken outside the regions of the brain where it's already naturally occurring, the potential for new therapies still exists. For instance, the hippocampus is where Alzheimer's disease causes most of its damage.

"The therapeutic angle is really based on the fundamental biology of the phenomenon," said Gage. "If you can understand how this process occurs, you can translate this process to an area of the brain that's damaged where you need this process to occur."

Gage also pointed out that the rate of neurogenesis increases when the adult mouse is physically active -- giving scientific credence to the old adage that exercise is a way to keep the gray matter nimble.

Psychological Science 2002;13:268-271.


Brain & Mind Magazine
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Copyright 2002 by State University of Campinas