New York Times-- Friday, October 15, 1999

Brain May Grow New Cells Daily
By NICHOLAS WADE

In a new challenge to the longstanding belief
that adults never generate new brain cells,
biologists at Princeton University have found
that thousands of freshly born neurons arrive
each day in the cerebral cortex, the outer
rind of the brain where higher intellectual
functions and personality are centered. 

Though based on research in monkeys, the
finding is likely to prove true of people,
too. 

If so, several experts said, it may overturn
ideas about how the human brain works and 
open new possibilities for treating degenerative
brain diseases. 

If the new brain cells, or neurons, are involved 
in memory and learning -- perhaps with each day's
batch of new cells recording that day's experiences
 -- scientists will have to make major revisions
in the longtime view that the adult brain's 
neurons are static in number and that memory is
stored only in the way they interconnect. 

In addition, if the brain's cells are in 
constant turnover, as the new finding suggests,
physicians may discover ways to use the brain's
natural regeneration system for replacing cells
that are lost in the diseases of aging. 

The discovery, by Elizabeth Gould and Charles 
G. Gross, is reported in Friday's issue of 
the journal Science. 

The belief that the adult brain does not 
make new cells rested on careful, well-known
studies by Pasko Rakic of Yale University, who
looked for the formation of new neurons in 
the monkey brain and found none. 

But the Princeton work is likely to be 
convincing, because it builds on previous
reports of brain cell turnover, notably by
Fernando Nottebohm of Rockefeller University,
who showed that canaries grow new neurons to
learn new songs, and recent studies showing
that new cells are formed in the hippocampus,
a brain region where initial memories of 
faces and places are formed. 

"The scientific community can easily
believe something it is 50 percent ready
to absorb, but not something that comes out of left
field," said Eric R. Kandel, a leading neuro-
scientist at Columbia University. "But here,
we are prepared for it." 

Kandel compared the likely change in view to
the paradigm shifts described by the historian
of science Thomas Kuhn as occurring when one
major scientific theory is replaced by another. 

Although the new study was done in macaque
monkeys and has yet to be confirmed in 
humans, as fellow primates monkeys are
usually quite predictive of what occurs
in people. 

Gould, who has studied new cell formation
in the hippocampus, and Gross, an expert
on the cerebral cortex, injected macaques
with a chemical that is incorporated in
the new DNA formed when a cell divides. 

They found that a stream of new neurons
were generated in the monkeys' brains in
a zone just above the brain's fluid-filled central
chambers. This zone was recently identified
by other scientists as the home of the brain's
stem cells, the source cells from which an
organ is replenished. 

The new neurons migrated toward the cortex,
matured and sent out axons to make connections
with other brain cells, the Princeton
biologists found. 

The researchers looked for new neurons in
four areas of the cortex, and found them
in three areas where memories are known to be
stored: the frontal cortex, used for decision-
making, and two areas on the side of the brain
used for visual recognition. 

No new neurons were detected in the fourth
area, the striate cortex, a region at the
back of the head that simply processes visual
information from the eyes and passes it on
to other parts of the cortex. 

Whatever the new cells are doing in the
cortex, they affect regions of the brain
that are central to human thought and identity.
The Princeton work, said Ronald D. G. McKay,
an expert on brain stem cells at the National
Institutes of Health, "places new neurons in
the region of the brain involved in the
highest level of personality: it's the
frontal cortex that is important in 
determining who you are in a very
human way." 

Gould said it was possible that the new
neurons arriving in the cortex would be
particularly sensitive to recording
information for a certain period while
they matured. 

"They would become integrated in the
circuitry and represent the information
being learned at that particular time,"
she said, after which they would not
record anything more. 

In other words, the conveyor belt of
new neurons might record successive days'
experiences almost like a moving tape. 

"We know the characteristic of memory is
that events are tagged with times," Gross
said. "We have no idea how that is done.
But since we have now shown there are new
cells added every day, which cover a
spectrum of ages, these cells could possibly
provide the substrate for the temporal
dimension of memory." 

Kandel, of Columbia University, said the
idea was perfectly possible, given how
little was now known about the brain's
system for ultimate long-term memory storage. 

"How do you distinguish the memory of 20
years ago from the memory of 30 years ago?
You would have to mark the birthday of the
cell in some way," Kandel said, suggesting
that the train of new neurons offered a
plausible mechanism whereby the brain might
somehow do this. 

The notion that new memories are stored
in a train of new nerve cells was advocated
in the 1960's by Joseph Altman, then of the
Massachusetts Institute of Technology. But
his proposal was not widely accepted. And
when Rakic, an authority on neuron formation in
the embryonic monkey brain, reported in 1985
that no new neurons were formed in the adult
monkey's brain, this became the accepted
view. 

Even when Gould and others showed recently
that new cells were formed in the 
hippocampus, Rakic argued that this was
a primitive area of the brain -- even
reptiles have a hippocampus -- and that
brain organs acquired more recently in
evolution, like the primates' cerebral
cortex, would not be expected to behave
the same way. 

Gould said it was this argument that
had made her determined to look for new
cells being formed in the cerebral cortex,
despite the expense of doing work on 
monkeys and the risk in "redoing an 
experiment that a very well respected 
person," Rakic, had already performed. 

Rakic's office said he was traveling
yesterday and unavailable for comment. 

If indeed the brain is constantly renewing
the cells in its cortex, hippocampus and
maybe other areas, the prospects for learning
how to repair the aged or damaged brain begin
to look much more hopeful. 
              
"Degenerative diseases of the brain are really
defined by loss of nerve cells," Kandel said.
Though diseases like Parkinson's affect specific
areas of the brain, it might become possible
to channel young new neurons into the areas
of disease. "This is pie in the sky," he said, 
"but at least there is now the possibility of
thinking about it." 

William T. Greenough, a neuroscientist at
the University of Illinois, said the Princeton 
work created a "whole new ball game" for
addressing brain diseases, by harnessing
the brain's own restorative potential. 

The Princeton biologists plan to follow
up their discovery by blocking the formation
of new neurons in monkeys' brains and seeing
what happens. If the new neurons are essential
for memory and learning, then serious deficits
should appear in the monkeys' performance. 

The researchers as yet have no idea whether
the loss of brain cells and the generation of
new ones are separate events or part of the
same cycle. 

"Our discovery," Gross said, "suggests more
questions than answers."

http://www.nytimes.com/library/national/science/
health/101599brain-princeton.html
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Victoria Nordli cg