[tt] Memory repair with stem cells

[Hughes, James J.]

http://www.eurekalert.org/pub_releases/2007-10/uoc--scc102507.php

Stem cells can improve memory after brain injury

Neural stem cells work by protecting existing cells and promoting
neuronal connections

Irvine, Calif. - New UC Irvine research is among the first to
demonstrate that neural stem cells may help to restore memory after
brain damage.

In the study, mice with brain injuries experienced enhanced memory --
similar to the level found in healthy mice -- up to three months after
receiving a stem cell treatment. Scientists believe the stem cells
secreted proteins called neurotrophins that protected vulnerable cells
from death and rescued memory. This creates hope that a drug to boost
production of these proteins could be developed to restore the ability
to remember in patients with neuronal loss.

"Our research provides clear evidence that stem cells can reverse memory
loss," said Frank LaFerla, professor of neurobiology and behavior at
UCI. "This gives us hope that stem cells someday could help restore
brain function in humans suffering from a wide range of diseases and
injuries that impair memory formation."

The results of the study appear Oct. 31 in the Journal of Neuroscience.

LaFerla, Mathew Blurton-Jones and Tritia Yamasaki performed their
experiments using a new type of genetically engineered mouse that
develops brain lesions in areas designated by the scientists. For this
study, they destroyed cells in the hippocampus, an area of the brain
vital to memory formation and where neurons often die.

To test memory, the researchers gave place and object recognition tests
to healthy mice and mice with brain injuries. Memories of place depend
upon the hippocampus, and memories of objects depend more upon the
cortex. In the place test, healthy mice remembered their surroundings
about 70 percent of the time, but mice with brain injuries remembered it
just 40 percent of the time. In the object test, healthy mice remembered
objects about 80 percent of the time, while injured mice remembered as
poorly as about 65 percent of the time.

The scientists then set out to learn whether neural stem cells from a
mouse could improve memory in mice with brain injuries. To test this,
they injected each mouse with about 200,000 neural stem cells that were
engineered to appear green under ultraviolet light. The color allows the
scientists to track the stem cells inside the mouse brain after
transplantation.

Three months after implanting the stem cells, the mice were tested on
place recognition. The researchers found that mice with brain injuries
that also received stem cells remembered their surroundings about 70
percent of the time - the same level as healthy mice. In contrast,
control mice that didn't receive stem cells still had memory
impairments.

Next, the scientists took a closer look at how the green-colored stem
cells behaved in the mouse brain. They found that only about 4 percent
of them turned into neurons, indicating the stem cells were not
improving memory simply by replacing the dead brain cells. In the
healthy mice, the stem cells migrated throughout the brain, but in the
mice with neuronal loss, the cells congregated in the hippocampus, the
area of the injury. Interestingly, mice that had been treated with stem
cells had more neurons four months after the transplantation than mice
that had not been treated.

"We know that very few of the cells are becoming neurons, so we think
that the stem cells are instead enhancing the local brain
microenvironment," Blurton-Jones said. "We have evidence suggesting that
the stem cells provide support to vulnerable and injured neurons,
keeping them alive and functional by making beneficial proteins called
neurotrophins."

If supplemental neurotrophins are in fact at the root of memory
enhancement, scientists could try to create a drug that enhances the
release or production of these proteins. Scientists then could spend
less time coaxing stem cells to turn into other types of cells, at least
as it relates to memory research.

"Much of the focus in stem cell research has been how to turn them into
different types of cells such as neurons, but maybe that is not always
necessary," Yamasaki said. "In this case, we did not have to make
neurons to improve memory."

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http://www.technologyreview.com/Biotech/19645/?nlid=638

Technology Review - Published by MIT

Wednesday, October 31, 2007

Saving Memories
Stem-cell transplants improve memory in brain-injured mice.

By Anna Davison

Using a clever new technique, researchers at the University of
California, Irvine, have shown that stem-cell transplants may improve
memory after brain injury, at least in mice. Their work adds to growing
evidence that stem cells might eventually help combat the devastating
memory loss associated with traumatic brain injury, Alzheimer's disease,
and stroke.

"It's a nice piece of work," says Jack Price, professor of developmental
neurobiology and director of the Centre for the Cellular Basis of
Behaviour at King's College London, who was not involved in the
research. "The challenge now is to go from those animal models into the
clinic."

Mathew Blurton-Jones and his colleagues at the University of California,
Irvine, genetically engineered mice so that they could trigger brain
damage only in the hippocampus, a region of the brain that's important
in spatial memory. They then transplanted neural stem cells into that
area. Three months later, those mice performed about as well on memory
tests as uninjured animals did.

"This is some of the more clear-cut evidence that you can improve memory
in a mouse--specifically memory--with stem cells," says Blurton-Jones.
The researchers describe their work in this week's issue of theJournal
of Neuroscience

Previous research has shown that stem-cell transplants can help restore
movement in animals after brain or spinal-cord injury. But the impact of
stem-cell transplants on cognitive function, which in many ways is more
complex than motor function, has been less clear, with different studies
yielding conflicting results. Part of the problem, says Blurton-Jones,
is that commonly used animal models involve extensive damage to the
brain, which "made it very difficult to dissect out what's going on."

It's still not clear, though, how the transplanted stem cells help. "The
question is, do they really, truly replace lost cells?" says Price.

Probably not. Blurton-Jones suspects that "the way our cells improved
the memory in mice was not by replacing those dead cells but by helping
to maintain those surviving cells." Several months after the stem-cell
transplants, he found more synaptic connections in the hippocampus of
treated mice compared with controls, as well as a slower rate of neuron
death.

"Our data are suggesting that stem cells can have a beneficial effect
that doesn't require them to take the place of dead cells,"
Blurton-Jones says. "They may be more versatile than we give them credit
for."

Boosting cell survival is likely to be a key component of future
stem-cell therapies, according to Arnold Kriegstein, director of the
Program in Developmental and Stem Cell Biology at the University of
California, San Francisco. "I doubt that we're likely to replace the
cells that are dying" in diseases like Alzheimer's or after brain injury
or stroke, he says. "But it may be possible to prevent them from dying."
Copyright Technology Review 2007.