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Stem cell therapy – a bird-brain idea?

The idea that new nerve cells can grow in adult brains forms the basis of current research into stem cell therapy. However, not so long ago, this idea was dismissed by most scientists. It took one man’s interest in canaries to change the way brains were viewed forever.

A fascination with birdsong

Fernando Nottebohm had been fascinated by the songs of birds for many years. He was struck by the similarity between human language and birdsong, noticing that birds were the only animals that attempted to do anything like what humans do vocally. Not even monkeys or apes, humans’ closest relatives, have such vocal range. In the 1980s, Nottebohm started studying the brains of canaries to see how they could learn to sing new songs every season.

Bird-brained

Nottebohm discovered that birdsong activated particular nerve cells in a bird’s brain – he called these “song nuclei”.

Nottebohm observed that the song nuclei of female canaries were different to males. Female canaries hardly ever sing, and their song nuclei were much smaller than the more vocal males. However, when treated with testosterone, females began to sing like males and their song nuclei grew. He also showed that the male canary song nuclei changed in size during the breeding season, when they start to sing more to attract females.

These last observations flew in the face of accepted wisdom. At the time, few scientists believed that an adult brain could produce new cells. So how were the song nuclei getting bigger?

Learning to sing a new tune

Nottebohm initially suggested that this swelling and shrinking of the song nuclei must be caused by the cells in this area changing size. However, he soon became convinced that this was wrong. He suggested instead that the canary brain was making nerve cells in the regions where they were needed, causing that region to get larger, while the cells in other areas were sacrificed, and those regions got smaller. Most of his colleagues thought this was a ridiculous idea.

To convince the rest of the scientific community that adult canary brains could grow new nerve cells, he needed proof, so Nottebohm designed an elegant experiment to prove his point.

Proving that canaries can grow new brain cells

Nottebohm injected canaries with radioactively-labelled thymidine. Thymidine is incorporated into newly made DNA, so any new cells made after injection would be radioactive. A month later, the canaries were killed and their brain tissue examined. Nottebohm and his team discovered large numbers of radioactive cells, many of which were nerve cells – new nerve cells were being made at an astonishing rate. The team wondered, could this regeneration be directed to heal damaged brain tissue?

The revolution begins

Despite having proved that new nerve cells were being produced all the time throughout the canary’s life, Nottebohm’s revolutionary ideas were not met with much excitement or even acceptance. Scientists questioned whether these changes were nerve cells and if they were functional. They dismissed the work as irrelevant to the human brain.

Adult neurogenesis in humans

In 1998, inspired by Nottebohm’s work, Fred Gage and his team at the Salk Institute found that adult human brains were also able to make new nerve cells. They injected cancer patients with a chemical called BrdU, which labels new dividing cells, and then analysed the brain tissue of five patients post mortem. All five showed evidence of recent, plentiful nerve cell division, or neurogenesis.

Implications for stem cell research

Suddenly, scientists could see the potential for using newly dividing brain cells to treat neurodegenerative disorders, such as Parkinson’s disease. If these stem cells could be delivered to the damaged part of the brain, maybe they would divide and specialise, replenishing the damaged tissue and restoring people to good health. The field of stem cell research was opened wide.

Written by Sara Loughnane, NZ Science, Mathematics, and Technology Teacher Fellow, 2006.

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