Brain Injury? Stem Cell Improve Memory

University of California - Irvine, November 2, 2007

Restoring memory after brain damage may be accomplished with the use of neural stem cells.  New UC Irvine research is among the first to demonstrate this.

Up to three months after receiving a stem cell treatment, mice with brain injuries experienced enhanced memory revealed the study data.  The progress was similar to the levels found in healthy mice.

Rescuing memory and protecting cells which were vulnerable to death, stem cells secreted proteins called neurotrophins say scientists.  To restore the ability to remember in patients with neuronal loss, drugs could be developed in the future that boost the production of these proteins.

"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."

Automatically developing brain lesions in areas designated by scientists, a new type of genetically engineered mouse was used by Tritia Yamasaki, Mathew Blurton-Jones, and LaFerla as they performed their experiments.  Selecting an area vital to memory formation and where neurons often die, the scientists destroyed cells in an area of the brain called the hippocampus.

Using mice with brain injuries as well as healthy mice, researchers tested memory by administering object and place recognition tests.  Memories of objects depend upon the cortex, and memories of place depend more upon the hippocampus.  Data from the object test revealed that injured mice remembered objects poorly about 65 percent of the time while healthy mice remembered them about 80 percent of the time.  Data from the place test revealed that mice with brain injuries remembered their surroundings just 40 percent of the time while healthy mice remembered their surroundings about 70 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.  In order to test this, stem cells were engineered to glow a greenish hue when exposed to ultraviolet light, then, 200,000 of these neural stem cells were injected into each mouse.  Following transplantation, the stem cells could be tracked by observing the colored cells under the light.

The mice were tested on place recognition three months after implanting the stem cells. Equaling the same level as healthy mice, mice with brain injuries remembered their surroundings 70 percent of the time after receiving stem cells.  Sustained memory impairments were observed in the control mice which did not receive any stem cells.

The behavior of the modified fluorescent green stem cells were observed next.  Indicating that the replacement of dead brain cells was not the manner in which memory was improved, the scientists found that only about 4 percent of them turned into neurons.  The cells congregated in the hippocampus, the area of the injury, in mice with neuronal loss.  Where as, the cells migrated throughout the brain in the healthy mice.  Intriguingly, more neurons were observed four months after transplantation in mice that had been treated, as opposed to mice that had been in the control group.

"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."

Scientists could try to create a drug that enhances the release or production of these proteins, if supplemental neurotrophins are in fact at the root of memory enhancement.  Efforts to differentiate stem cells into other types of cells, at least in terms of memory research, could be more relaxed.

"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."

The Journal of Neuroscience has published the results of the study in their October 31st issue.

UCI scientists Debbi Morrissette, Masashi Kitazawa and Salvatore Oddo also worked on this study, which was funded by the National Institute on Aging, the National Institutes of Health, and a California Institute for Regenerative Medicine postdoctoral scholar award.