Is it possible to let brain cells grow back?

Researcher lets brain cells grow back

Magdalena Götz made a discovery that many colleagues could hardly believe. But she was right and now wants to develop a therapy to replace lost brain cells.

In 1999, a 36-year-old woman amazed her colleagues at the international annual meeting of neuroscientists. She claimed that the glial cells, the previously neglected supporting cells of the brain, can transform into nerve cells. “Not possible,” was the reaction of many established brain researchers.

There was a headwind, especially from the "alpha men", recalls Magdalena Götz. But the petite scientist, who speaks in a loud voice and also hits the table once to underline her statements, countered confidently: She did not present any results that she was not convinced of. In the meantime, their revolutionary idea has found its way into textbooks. And Götz is working on using the potential of these constantly growing glial cells to replace lost nerve cells. This would open completely new doors to medicine in the treatment of brain diseases such as dementia or a stroke.

Design and lend a hand

Magdalena Götz is sitting on an office chair, has her right foot under her and is playing with a strand of hair before she starts drawing a graphic on paper with a few lines, glial cells on the left, nerve cells on the right - highly concentrated, fast and determined. It's not difficult to imagine the 54-year-old biologist as a curious teenager.

"Whenever she had a goal in mind, she has always done everything to implement it to perfection," says her father Lothar Götz, professor emeritus for architecture. He remembers Magdalena designing and tailoring a dress as a teenager to enter a competition. She won, moved her design to the national competition and finally to London to the European competition, where she also won. The motive “to pursue an idea with courage and perseverance” runs through it, regardless of who you ask about Magdalena Götz.

She stood in the laboratory and followed her thing, explains Jürgen Bolz, in whose work group Magdalena Götz wrote her diploma and doctoral theses. Magdalena was the only woman in the “Bolz Gang”, as the seven-person research team at the Friedrich Miescher Laboratory of the Max Planck Institute in Tübingen called themselves. The gang worked together, sometimes lived together and also celebrated together. Magdalena Götz remembers that they met in the summer in Reusten, a small town near Tübingen, played with lighted Frisbees and celebrated practically all night long. They have already had their fun, she says, as if to dispel concerns that there was no time for exuberance in view of her jam-packed résumé.

"There was headwind, especially from the 'alpha men'."

At the age of 35 she became a group leader at the Max Planck Institute for Neurobiology in Munich, three years later she qualified as a professor, and at the age of 42 she became director at the Institute for Stem Cell Research at the Helmholtz Center in Munich and at the same time held the chair for Physiological Genomics at Ludwig -Maximilians University of Munich. She was honored with six prizes, including the Gottfried Wilhelm Leibniz Prize endowed with 2.5 million euros.

A little braver than others

Bolz, now a professor at the University of Jena, recalls that she was perhaps a little braver than others and dared to experiment with uncertain results. And she had an eye for discoveries that others might have overlooked. In her doctoral thesis, she researched how nerve cell fibers grow from the eye into the cortex during brain development. Once a piece of tissue from the cerebral cortex accidentally lay the wrong way round in the culture dish. Others might have thrown it away. But Magdalena looked closely. She noticed that the growing nerve cell processes no longer took the direct route. Instead, they made a 180-degree turn to reach their regular goal in the wrong-way tissue. At the time, they provided evidence that nerve cells reach their destination using chemical signals, that is, they smell it, says Bolz.

After completing her doctoral thesis, the scientist does not let go of one question: Is there a common precursor cell from which different types of nerve cells are formed? Jack Price of the National Institute of Medical Research in London was one of the few researchers who worked with a technique that made such an investigation possible. So Magdalena Götz begins in Price's laboratory in London. After three and a half years there is an abrupt end, which shows how closely Götz is connected to her research. Because for her work she needs mice with a certain abnormal development in the cerebral cortex. When the mouse transport threatens to fail due to technical hurdles, she unceremoniously moves to her mice in Göttingen.

Shaken dogma

There she lays the foundation for her first groundbreaking discovery. In an unspectacular control experiment, she stains the cells of the developing mouse brain. Based on the knowledge available at the time, one would have expected to find both radial glial cells - a special type of glial cell - and precursor cells for nerve cells. She only wanted to stain the glial cells with a marker, she says, but then saw that all the cells were stained. As a result, there is still no clear differentiation between the two in the developing brain. This led her to the question of whether radial glial cells might be neuronal progenitor cells.

A little later she tries to clarify this in her own laboratory at the Max Planck Institute for Neurobiology in Martinsried. In 1997 she was able to confirm her suspicion. The discovery, however, is also a priority for someone else. On the website of Arnold Kriegstein, stem cell researcher at the University of California, it says: We discovered that radial glial cells are neural stem cells. While Magdalena Götz demonstrated the process in the culture dish, Kriegstein's team succeeded in the brains of rats. But Magdalena was the first, says the stem cell researcher Price, who is currently writing a book about "brain repair" and is keeping an eye on the details.

When she took over the chair for Physiological Genomics at the University of Munich in 2004, it opened up a new field for her, says the scientist - the field of brain injuries. With this, the idea of ​​awakening the potential of sleeping cells to compensate for brain injuries came more into focus. However, the brain itself seems to inhibit this potential. Her team showed that glial cells simply stay what they are after an injury in the mouse brain. It was only when the researchers transferred the cells from the brain into a culture dish that some glial cells finally turned into nerve cells.

In order to repeat the success in the culture dish in the living brain, the researchers sent harmless viruses into the cells. These activated various genes that are normally only active during early brain development. The glial cells then transformed into nerve cells - they were successfully reprogrammed. Initially, the team only succeeded in ten percent of the treated glial cells. Only when the researchers used another trick and activated a protein that helps the glial cell to master the demanding transition to the metabolism of a nerve cell were they able to increase the conversion rate to 90 percent, as they recently reported in the journal Cell Stem Cell.

A way with pitfalls

Every insight brings Götz to a new question. Can the newly formed nerve cells replace the lost ones with all their functions? Their latest data indicate that immature nerve cells transplanted from the embryonic cortex into the injured region of an adult mouse actually work after a few weeks as they should for nerve cells at this point. For example, a cell placed in the visual center of the brain reacts to orientation stimuli.

But Götz is thinking of reprogramming the glial cells that are already in the brain. It remains to be seen whether this will also lead to functional nerve cells. The long-term goal is to restore the brain's ability to regenerate after an injury. Then, for example, stroke patients with visual disturbances could see better again and Parkinson's patients could move better again.

But there is still a long way to go before their research can really be applied in the clinic. Götz does not expect that she will experience this success during her professional life. Many researchers point out that the neurosciences have aroused great expectations for decades, but hardly provide any tangible therapies.

Intervention could be harmful

Sebastian Jessberger from the Institute for Brain Research at the University of Zurich points out a possible problem with Götz's approach. The basic idea of ​​creating new nerve cells is fantastic. But the incomplete regenerative capacity is presumably the price our brain has to pay for its high level of complexity and performance, he says. For example, nerve tissue that has scarred after an injury can protect against further damage. But if you now artificially ensure the creation of new nerve cells, this could also worsen the disease. Experience with the transplantation of stem cells into the brains of Parkinson's patients shows that new nerve cells can sometimes have negative effects and, for example, aggravate movement disorders.

Does Götz 'method run counter to the protective mechanism of the brain established by nature, and does it possibly open Pandora's box in our highly complex thinking organ? No, says the researcher. Humans therefore do not produce regenerative nerve cells because there was no selection pressure for this in their evolution. The only exception in our brain is the hippocampus, an important place for memory formation. New nerve cells would develop there throughout life. Still, no one gets more stupid about it, she says. There is no good reason to argue against reactivating the ability to regenerate, even if the majority of researchers believe it. Magdalena Götz does not lack the courage and perseverance to track down this reactivation, as her previous successes show.