Study Shows Novel Way to Trigger New Neuron Production in the Aging Brain

DURHAM, N.C. -- Researchers have shown for the first time that putting two specific types of neural cells directly into an aging brain can kick-start creation of brain cells linked to learning and memory.

It has been shown over the last decade that brain cells replicate, a finding that had run counter to previously accepted dogma. The area where neuron-forming stem cells perform much of this replication is the hippocampus, part of the brain linked to memory and learning, and an area affected in older people as well as those with Alzheimer’s disease. Scientists are now exploring how brain cells replicate – a process called neurogenesis – and how to improve this when it appears to slow or stop all-together.

In older people and people with Alzheimer’s disease “neural stem cells are sitting there but not dividing, so they are not making new neurons,” said Ashok K. Shetty, Ph.D., professor of neurosurgery at Duke and medical research scientist at the Durham Veterans Affairs (VA) Medical Center. “We hope that by making more neurons, we can improve learning and memory” in compromised patients.

Shetty and colleagues have shown that implanting specific brain cell precursors into the hippocampus region of aging rats increases neurogenesis, a first step in working toward therapies for humans. The results of their work appear in the August issue of the journal Stem Cells.

Two types of cells were harvested from the spinal cords of rats and then grafted into the aging rat hippocampus. After three weeks researchers saw an increase in neurogenesis in the rats that received the cell implants compared to rats that did not receive any treatment and rats that received implantation surgery but not receive stem cells. This is the first evidence that introduction of these two kinds of neural stem cells stimulate neurogenesis in the hippocampus.

The hippocampus has been linked to not just memory formation and storage in the brain, but also depression and neurodegenerative diseases such as Alzheimer’s.

“Any strategies for improving neurogenesis in aging animals may be helpful to humans,” said Shetty. The research was supported by the National Institutes of Health (NIH) National Institute on Aging as well as the National Institute of Neurological Disorders and Stroke and the Department of Veterans Affairs.

The researchers believe that the precursor cells secreted nerve growth factors that stimulated the inactive stem cells of the aging hippocampus to start dividing again. They also did a study that injected nerve growth factors directly to see if they would stimulate neurogenesis. Publication of study results is expected by the end of the year.

Shetty said researchers next plan to do a similar study to see if the grafting causes increased neurogenesis on a long-term basis, and if the increase in cell generation can impact learning and memory.

The first author of this study is Bharathi Hattiangady, Ph.D., a research associate in the department of surgery at Duke and medical research scientist at the VA Medical Center in Durham, N.C. Another member of the Duke/VA team is Bing Shuai, M.D. The other collaborators include Jingli Cai, Ph.D., Turhan Coksaygan, Ph.D., and Mahendra S. Rao, Ph.D., all in the Stem Cell Unit of the National Institute on Aging at the NIH at the time of the study.