Adult Human Brains Add New Cells.

Offering hope that brain cells slain by stroke, disease, or injury are replaceable, five cadavers have presented scientists with the first solid evidence that nerve cells continue to be born throughout life in the human brain.

The new study, described in the November NATURE MEDICINE, challenges the long-held doctrine that an adult human brain cannot form new nerve cells, or neurons, the information-processing cells of the brain. Scientists had crafted a plausible explanation for that dogma: Higher animals, especially people and other primates, might be so dependent upon learned skills and memories encoded in their neural circuits that their brains don't dare grow new neurons that might disrupt those imprints.

"You would have new cells that never went to elementary school," notes Pasko Rakic of Yale University School of Medicine in New Haven, Conn.

Yet, evidence that the brains of mature animals develop new neurons has gradually emerged. Most of the research has focused on the hippocampus, a brain region normally involved in learning and the processing of memories. In birds, mice, and other animals, scientists have clearly documented the birth of hippocampal neurons throughout life. Earlier this year, researchers finally extended that observation to primates, showing neuron birth in adult marmoset monkeys (SN: 3/21/98, p. 180).

Investigators have now used the tragedy of cancer to find similar evidence in people. Although the chemicals used to label newborn cells in the animal experiments are toxic, physicians administering chemotherapy to cancer patients occasionally use them to monitor tumor growth. The chemicals, such as bromodeoxyuridine, or BrdU, become part of newly formed DNA when dividing cells copy their genetic information. Researchers, for example, can then identify any cell with BrdU in its DNA as a recent arrival.

Peter S. Eriksson of Goteborg University in Sweden persuaded a physician using BrdU on people with cancer of the tongue or larynx to ask the family, whenever a patient died, if he could remove brain sections for study. Since 1996, Eriksson has received such permission five times and quickly obtained the needed brain material, before it deteriorated.

Working with a research team led by Fred H. Gage of the Salk Institute for Biological Studies in La Jolla, Calif., Eriksson's group examined slices of the hippocampus, focusing on an area called the dentate gyrus, where neuron birth occurs in other adult animals. The researchers identified BrdU-labeled cells and stained the brain region with antibodies that distinguish neurons from other kinds of brain cells. In the five people, whose ages at death ranged from 57 to 72, there were sometimes more than 200 new, healthy neurons per cubic millimeter of dentate gyrus, the scientists report. Gage estimates that 500 to 1,000 neurons are born in the gyrus each day--a small fraction of the many millions already there.

"It's wonderful, it lays to rest, finally, a controversy that I think has really blocked progress in understanding what these new neurons might be doing," says Elizabeth Gould of Princeton University, who led the marmoset work.

Some controversy lingers, however. Rakic maintains that neuron birth in adults is a limited phenomenon, perhaps occurring only in the dentate gyrus. Gould counters that the no-new-neurons dogma has stopped scientists from thoroughly testing whether neuron birth occurs elsewhere in the brain. "We need to find out how widespread this phenomenon is," she says.

Gage notes that scientists must now factor neuron birth in adults into their thoughts about plasticity, the ability of the brain to reshape its neural circuits throughout life. Potentially even more important--if investigators can understand why parts of the adult brain do or do not grow new neurons--is the possibility of inducing cell proliferation to replace dead neurons in people who have suffered strokes or who have neurodegenerative illnesses such as Alzheimer's or Huntington's diseases.