The birds that had spent their time flying free had more new
neurons in the hippocampus than the birds kept captive did. But
Nottebohm didn’t know what factor led to the increase in neuron production.
Follow-up work in Gage’s lab found that mice living in cages
with running wheels—which all rodents will spin for hours every
night—made more new neurons than did rodents in identical cages
without wheels.
Exercise—whether by wing or foot—spurred neurogenesis, it
seemed (SN: 2/25/06, p. 122).
Gould then delved deeper into the stress-neurogenesis connection. She and her team set up a colony of marmosets, which are petite
primates with funky hairdos. They tested
the effects of social stress on neurogenesis by placing marmosets that were
unfamiliar with each other in the same
cage. Sure enough, the stressed marmosets produced fewer new neurons
than did marmosets left on their own.
Gage reported similar findings in mice.
In the past 5 years, piles of scientific
papers have continued to identify other
factors that affect neurogenesis. A bigger picture formed: Nonstressful stimulation and exercise, as well as certain
hormones, growth factors, and drugs,
speed the birth of neurons, while stress,
aging, and sleep deprivation slow the
process. Taken together, the recent
studies indicate that neurogenesis is
“not a genetically preprogrammed
process where cells are born and give PLUCKY PRIMATE— A marmoset prepares to
rise to new neurons at a sort of regular leap in a playground filled with ladders and food
clip,” says Gage. “Instead, there’s this for foraging. Elizabeth Gould of Princeton University
concept that [new neurons] are regu- studies the effects of enriched environments such
lated by experience.” as this one on the brains of mammals.
As interest in the field grew, a more
basic question came into focus: What does it mean?
“The most central point in the field is what the cells are good
for,” says Hongjun Song, a neurogenesis researcher at Johns Hopkins School of Medicine in Baltimore. “We know that all mammals
have the new cells. So why do we need them? If we don’t have
them, what’s going to happen?”
ulation, they wither and die. “It seems that something is coded in
those [new] cells during that critical period,” says Gage. He says
he thinks that this ability makes new information more prominent. Consensus is building that “the new neurons are doing something important for learning,” says Gould. In rodents, for instance,
neurogenesis appears crucial for spatial memory, needed in tasks
such as remembering how to navigate a maze.
HARNESSING NEW NEURONS Even as researchers uncover
how the brain generates new cells and how these cells knit themselves into the brain’s networks, companies are already testing compounds for their ability to stimulate neurogenesis.
“If we have new neurons, can we use
them to remake [brain] circuitry and to
cure disease?” asks Song.
Drugmakers’ interest grew in 2000,
when a team at Yale University reported
that antidepressants such as fluoxetine
(Prozac) increased neurogenesis in the
hippocampi of rats. The finding helped
explain how the drugs work. While antidepressants boost neurotransmitter levels immediately, patients don’t feel better for several weeks, which puzzled
psychiatrists. But because new neurons
don’t mature in the hippocampus until
several weeks after the start of drug
therapy, the Yale team speculated that
they may have stumbled on the real way
antidepressants work.
A series of follow-up experiments by
René Hen and colleagues at Columbia
University buttressed the theory. The
team treated mice with antidepressants
but inhibited neurogenesis by zapping
the animals’ brains with X rays. Minus
neurogenesis, the animals didn’t
THE WHAT AND THE WHERE It turns out that what new
neurons do depends on where they end up. Many arise from a
reservoir of brain stem cells near the ventricles, the fluid-filled
openings in the middle of the brain. Most then migrate to the
olfactory bulb on the underside of the brain, where they presumably help in odor detection.
Some researchers say that they’ve found small stashes of brain
stem cells and modest neurogenesis throughout the brain. But
those results remain controversial. Only in the ventricles and the
hippocampus, especially in a substructure called the dentate gyrus,
are researchers confident that brain stem cells regularly spin off
new neurons. Given the hippocampus’ key role in memory, scientists zeroed in on it from the beginning.
GOULD/PRINCETON UNIV.
At first, neurogenesis researchers thought that new neurons
might simply replace old, dying ones. “But the view is changing,”
says Song, “because it’s almost impossible for the young cells to
make exactly the same connections as the cells [that die]. What
we’ve found, and what other people have found, is that the young
cells seem to be different than the old cells. … The young cells are
very plastic, they’re very flexible.”
Like babies exploring the world, young neurons in the dentate
gyrus spend their first weeks absorbing information that programs
them for the rest of their existence, according to a theory Gage
and others are developing. If the nascent cells are starved of stim-
respond to the drugs.
“[T]hat’s what got us convinced that neurogenesis had something
to do with the mechanism of action of antidepressants,” says Hen.
Recent work in monkeys lends further support to the idea.
In a paper published in the May 2 Journal of Neuroscience, a
team led by Tarique Perera of Columbia University found that
electroconvulsive shock therapy, a last-resort treatment for
depression in people, boosts neurogenesis in adult monkeys.
The study is the first to show that depression treatment
increases neurogenesis in primates.
Researchers are now exploring whether boosting neurogenesis
in brain areas other than the hippocampus might benefit patients
with Alzheimer’s, Parkinson’s, and other diseases. “There is increasing evidence that there are dormant [brain stem cells] in different parts of the brain, and with proper stimuli these quiescent cells
can be woken up [to] start producing neurons,” Hen says. Whether
this will help patients remains unknown.
A Swedish company, NeuroNova, plans to test the idea in people late this year. Using an undisclosed growth factor, the company hopes to induce neurogenesis and other brain changes to
restore function in patients with Parkinson’s disease. The growth
factor will be delivered via a tube directly into the brains of 10 to
20 patients with advanced Parkinson’s, says Anders Haegerstrand,
NeuroNova’s chief scientific officer. “We’ve done experiments [in
animals] where we see an increase in dopamine cells”—a type of
neuron—“in the substantia nigra,” he says, referring to the brain
structure that degenerates in Parkinson’s patients.
But there’s a danger. Stimulating too much neurogenesis willy-nilly can cause seizures, says Phyllis Wise, who studies animal
models of stroke at the University of Washington in Seattle. In
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