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A New Wrinkle on Our Gray Matter

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TIMES SCIENCE WRITER

In the singular cells that give rise to the mind, researchers are discovering provocative evidence of the brain’s unexpected ability to renew itself.

Contrary to long-standing belief, people keep growing new brain cells well into old age, recent research suggests. One energizing effect of learning may be to spur the growth of new brain cells, while helping others to survive longer, animal experiments show.

As researchers announced earlier this week, even regular jogging may spur the growth of new brain cells.

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Together, these new insights raise hopes that doctors might someday be able to mend minds damaged by disorders such as Parkinson’s and Alzheimer’s with treatments that stimulate the growth of additional neurons. By seeding the brain with new cells, doctors also might be able to replace nerve tissue damaged by birth defects, injury or stroke.

Eventually, they suggest, they might even be able to stave off the mental effects of aging or devise more effective educational techniques to promote learning.

“It is potentially revolutionary,” said William Thies, vice president for medical and scientific affairs at the Alzheimer’s Assn., which has funded some of the research.

Experts caution that no one knows what these new cells actually do in the human brain, or whether they even become part of functional neural circuits where they could affect behavior and thought. The new cells have been detected only in one part of the brain called the hippocampus, which is involved in learning and memory.

Even so, scientists say the findings herald a new era in brain research.

“The door has been opened,” said neurobiologist Fred H. Gage at the Salk Institute for Biological Studies in La Jolla. “This field is exploding.”

Until recently, neuroscientists were convinced the brain stopped producing any new nerve cells at birth. While the connections between neurons might rise and fall dramatically during a lifetime, the number of brain cells was thought to be fixed.

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Researchers speculated that nature had designed the brain that way because any new neurons would disrupt the patterns of cells and synapses in which memories are stored and which form the support structure of thought.

Overturning a century of conventional wisdom about the central nervous system, Gage and his colleagues at the Salk Institute found that the human brain can replenish itself by growing new neurons, even among the elderly.

“Most of us learned in medical school that nerve cells simply do not reproduce in the brain. That was the dogma,” said Dr. Ira Black, a neuroscientist at the Robert Wood Johnson Medical School. “This is exciting new information suggesting that . . . might not quite be true.”

An Unexpected Discovery

Gage, in collaboration with Dr. Peter Ericksson of Sahlgrenska University Hospital in Sweden, detected the new neurons in the hippocampus. The cells were growing at a rate of perhaps hundreds of new cells every day.

In research reported late last year, the scientists found the new cells by examining samples of brain tissue from a small group of patients who had died of cancer. As part of their chemotherapy, the patients had been treated with an unusual chemical called Bromodeoxyuridine, which is absorbed only by dividing cells.

When the researchers detected the chemical in neurons of the hippocampus, they could only conclude that new brain cells must have been growing.

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“Our study is important to the extent that it demonstrates that new neurons are being born in humans,” Gage said. “But we don’t know whether or not the new neurons are functioning.”

Even so, Gage’s findings were enough to convert one of the dogma’s staunchest defenders. Dr. Pasko Rakic, a leading expert on neurons at Yale University, said, “I was one of those who were skeptical. But this is very exciting.”

Indeed, Rakic recently reported that, for the first time, his own lab had detected the growth of new neurons in the brains of adult macaque monkeys.

His work is one in a series of new findings about neurons reported at research meetings in recent months that have scientists rethinking the brain’s unique gray matter.

Researchers have discovered that brain cells:

* Double their number after birth, especially during the first six years of life. An analysis by William Shankle, a cognitive neuroscientist at UC Irvine, suggests that the new neurons appear in each of the six layers of the brain’s neocortex as infants and young children develop.

* Continue to grow in the brains of many adult mammals, including three species of primates, reinforcing the likelihood that it happens in people too. Princeton University expert Elizabeth Gould, who conducted the new research, said the young adult monkeys produced thousands of new brain cells every day. The number of new cells being produced declined dramatically only in the oldest monkeys, Gould said. Researchers now wonder if some mental effects of aging, such as memory loss, may be related to a defect in the brain’s previously unsuspected ability to grow new cells.

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* Are kept alive by exercise and even stimulated to grow new neurons. Gage and his colleagues recently reported that adult mice living in an enriched environment that included running wheels, tunnels, treats and toys not only improved their learning ability, but also doubled the number of new brain cells in the hippocampus region. Regular exercise, in this case by running in the wheel, spurred the growth of new neurons in mice, Gage reported.

* May benefit especially from learning tasks that exercise the hippocampus. Under normal conditions, new neurons in the hippocampus usually die within two weeks. But memory and motor-control tasks that stimulate the hippocampus more than doubled the number of neurons that survive, from about 3,000 to 7,000, within a day, Gould’s team at Princeton recently reported. Learning may profoundly alter the structure of the adult mammalian brain at the cellular level, they said.

The findings are especially important because they offer proof that, at the level of basic biology, all brains work in much the same way, whether the species is a rat, a tree shrew, a monkey or a human being.

“This presents the likelihood that studies performed in rodents have a lot of relevance to primates, including humans,” Gould said.

That gives greater scientific weight to animal studies that have demonstrated the killing effects of stress on brain cells and the enriching neural influences of learning and stimulating surroundings.

“This work opens the door to studying the effects of experience,” Gould said, “to doing experiments in animals with direct relevance to humans.”

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Brain Gain

People keep growing new brain cells well into old age, recent research suggests. The new cells turn up in the hippocampus, which is key to forming new memories.

But so far, no one knows what the new cells do or whether they even become part of functional neural circuits where they could actually affect behavior and thought.

The brain relies on many different kinds of neurons linked in a network of 100 billion cells, as the building blocks of thought, emotion, motor control and the senses.

Unipolar neuron:

Has the simplest design and is found mostly in nerves devoted to smell, taste, hearing and other sensory information. Its cell body (dark circle) does not participate much in conducting signals.

Pyramidal neuron:

Is the most common type of neuron. Has two widely separated sets of dendrites and axon branches linking back to them.

Stellate neuron: Found in the cerebral cortex and areas of the brain stem and spinal cord. In the cerebral cortex they handle local processing and send messages to other nearby cells.

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NEURON ANATOMY

Neurons are the special nerve cells that make up the central nervous system and the brain. A neuron may both receive and send out electrical signals to neighboring neurons.

A single axon conveys electrical signals to other neurons, and numerous hair-like structures called dendrites receive incoming signals.

Glomerular neuron: Found in the olfactory bulb above the nasal cavity. Glomerular neurons lack axons. They convey nerve signals in the form of small voltage changes in their membranes.

Golgi neuron: Plays a role in fine movement. Found in the cerebellum.

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