DURHAM, N.C. -- Neurobiologists have discovered why the
aging brain produces progressively fewer new nerve cells in its
learning and memory center. The scientists said the finding,
made in rodents, refutes current ideas on how long crucial
"progenitor" stem cells persist in the aging brain.

The finding also suggests the possibility of treating
various neurodegenerative disorders, including Alzheimer's
disease, dementia and depression, by stimulating the brain's
ability to produce new nerve cells, said senior study
investigator Ashok K. Shetty, Ph.D., professor of neurosurgery
at Duke University Medical Center and medical research
scientist at Durham VA Medical Center.

Results of the study appear online in the journal
Neurobiology of Aging. The research was funded by the National
Institutes of Health and the U.S. Department of Veterans
Affairs.

Previous studies by Shetty and others had demonstrated that
as the brain ages, fewer new nerve cells, or neurons, are born
in the hippocampus, the brain's learning and memory center. In
one study, Shetty and colleagues showed that the production of
new neurons in rats slows down dramatically by middle age --
the equivalent of 50 years in humans.

But scientists did not know what causes this decline.

The common assumption had been that the brain drain was due
to a decreasing supply of neural stem cells in the aging
hippocampus, said lead study investigator Bharathi Hattiangady,
Ph.D., research associate in neurosurgery. Neural stem cells
are immature cells that have the ability to give rise to all
types of nerve cells in the brain.

In the current study, however, the researchers found that
the stem cells in aging brains are not reduced in number, but
instead they divide less frequently, resulting in dramatic
reductions in the addition of new neurons in the
hippocampus.

To conduct their census, the researchers attached
easy-to-spot fluorescent tags to the neuronal stem cells in the
hippocampus in young, middle-aged and old rats.

They found that in young rats, the hippocampus contained
50,000 stem cells -- and, significantly, this number did not
diminish with aging. This finding, the researchers said,
suggested that the decreased production of new neurons in the
aged brain was not due to a lack of starting material.

The researchers then used another fluorescent molecule to
tag all stem cells that were undergoing division in the process
of staying "fresh" in case they were recruited to become mature
nerve cells.

They found that in young rats, approximately 25 percent of
the neural stem cells were actively dividing, but only 8
percent of the cells in middle-aged rats and 4 percent in old
rats were dividing. This decreased division of stem cells is
what causes the decreased neurogenesis, or birth of nerve
cells, seen with aging, the scientists said.

"This discovery provides a new avenue to pursue in trying to
combat the cognitive decline associated with conditions such as
Alzheimer's disease and with aging in general," Hattiangady
said.

The team now is searching for ways to stimulate the brain to
replace its own cells in order to improve learning and memory
function in the elderly.

One approach being explored is to treat older rats with
drugs designed to mimic the action of compounds called
neurogenic factors, which encourage stem cells in the brain to
divide, Shetty said. The researchers also are grafting neural
stem cells grown in culture dishes into the hippocampus, to
stimulate those already present. Additional approaches include
using behavioral modification techniques, such as physical
exercise and exposure to an enriching environment, that are
known to stimulate proliferation of stem cells.