Living proof exercising the brain helps it function, provides clues to improving stem cell therapy

We have long known the brain is not static. Parts of it change and become stronger in response to being stimulated. This “plasticity” as it is called, is generally attributed to changes in the nerves themselves. But a CIRM-funded Stanford team now has proof that strengthening the insulating myelin that wraps the nerves may have a critical role in this plasticity. Think of it as improving the roadbed for the signals being sent along the nerve highway.

A few recent studies have suggested this role for myelin, but they have looked at nerves growing in a lab dish. The tests that could have proved this is really happening in living animals have been too invasive until now. The Stanford team, led by Michelle Monje, used a new technique called optogenetics to make the connection in living mice. The procedure inserts the genes for light-sensitive neural switches into specific nerves. Those nerves then fire when researchers expose them to certain wavelengths of light. Because the light can diffuse through the brain from the surface, no invasive probes are necessary.

In this case, the light became the brain’s exercise bike. The nerves that had the added gene were the motor nerves, and after a period of stimulation the researchers saw myelin growth and in the following weeks improved muscle function in the mice.

Monje’s team attributed the improved myelin status to activity of a type of cell called an oligodendroctye precursor cell, which is the type of brain cell many stem cell scientists target for transplanting into patients. In stem cell therapy, many researchers consider it better to transplant these middle-man cells created from stem cells rather than the stem cells themselves. The current study gives the stem cell community ways to think about improving the results after transplant. Following up with brain stimulation may be important.

A press release from Stanford quotes Monje on the broad implications for her finding:

“Myelin plasticity is a fascinating concept that may help to explain how the brain adapts in response to experience or training. . . and future work on the molecular mechanisms responsible may ultimately shed light on a broad range of neurological and psychiatric diseases.”

In the CIRM-funded project using these findings, Monje’s goal is to find small molecules that could stimulate the activity of the oligodendrocyte precursor cells in patients who have undergone chemotherapy and are experiencing the mental decline dubbed “chemo brain.” The researchers’ findings are described in a paper that was published online today in Science Express.

Don Gibbons

CIRM funding: RN3-06510