Exercise Stimulates Nerve Growth via Muscle Signals

We know that exercise benefits our bodies. But could it also help our nerve cells grow?

A recent study from The Massachusetts Institute of Technology (MIT), published in Advanced Healthcare Materials, reveals that exercise may stimulate neuron growth, not only through biochemical signals but also through the physical effects of muscle contraction. The results could create new opportunities for developing nerve repair therapies.

Muscles talk back to nerves

Exercise is widely recognized for its benefits on our physical health – such as strengthening muscles, enhancing cardiovascular function and supporting the immune system. While these positive effects on organs and tissues are well-documented, the specific impact of exercise on nerve cells is not as well  explored.

Given that nerves control muscle movement and relay vital information throughout the body, understanding how exercise influences neurons could lead to new therapies for nerve injuries and neurodegenerative diseases.

In 2023, a study by Dr. Ritu Raman, the Eugene Bell Career Development Assistant Professor of mechanical engineering at MIT and corresponding author of the recent paper, hinted at biochemical connections between muscle activity and nerve health. Raman discovered that implanting muscle tissue at a site of traumatic muscle injury and then exercising the new tissue by stimulating it repeatedly with light, could restore mobility in mice. When the researchers examined the graft, they found that regular exercise prompted the grafted muscle to generate specific biochemical signals known to encourage the growth of nerves and blood vessels.

“That was interesting because we always think that nerves control muscle, but we don’t think of muscles talking back to nerves. So, we started to think stimulating muscle was encouraging nerve growth. And people replied that maybe that’s the case, but there’s hundreds of other cell types in an animal, and it’s really hard to prove that the nerve is growing more because of the muscle, rather than the immune system or something else playing a role,”

Dr. Ritu Raman

Exercise provides biochemical benefits

In the new study, Raman and colleagues conducted two experiments to explore how exercise affects neuron growth. They grew genetically-modified mouse muscle cells and used light to stimulate these cells to contract, mimicking exercise. This caused the muscles to release a mixture of biochemical signals known as myokines, which they collected in a solution. They then exposed motor neurons to this solution and observed the impact.

“I would think of myokines as a biochemical soup of things that muscles secrete, some of which could be good for nerves and others that might have nothing to do with nerves. Muscles are pretty much always secreting myokines, but when you exercise them, they make more,”

Dr. Ritu Raman

The neurons exposed to myokines grew four times faster than those that weren’t. “They grow much farther and faster, and the effect is pretty immediate,” Raman added.

The effects of physical stimulation on nerve cells

“Neurons are physically attached to muscles, so they are also stretching and moving with the muscle. We also wanted to see, even in the absence of biochemical cues from muscle, could we stretch the neurons back and forth, mimicking the mechanical forces (of exercise), and could that have an impact on growth as well?” said Raman.

Next, the team grew neurons on a mat embedded with tiny magnets and used an external magnet to gently stretch the neurons, simulating the mechanical forces they would experience during exercise. They “exercised” neurons like this for 30 minutes a day. Surprisingly, this mechanical stretching led to neuron growth comparable to that seen in the biochemically stimulated neurons.

“That’s a good sign because it tells us both biochemical and physical effects of exercise are equally important,” Raman noted.

A genetic analysis of the neurons revealed that both biochemical and mechanical stimulation enhanced the expression of certain neuronal genes, which are associated with nerve maturity and improved communication between nerves and muscles.

“We saw that many of the genes up-regulated in the exercise-stimulated neurons were not only related to neuron growth, but also neuron maturation, how well they talk to muscles and other nerves and how mature the axons are. Exercise seems to impact not just neuron growth but also how mature and well-functioning they are,” Raman said.

Exercise as medicine

These findings open the door to new exercise-based therapies for nerve repair, especially for patients with nerve injuries or neurodegenerative diseases like amyotrophic lateral sclerosis. Harnessing this “muscle–nerve crosstalk” connection could lead to innovative treatments aimed at healing damaged nerves by promoting neuron recovery through muscle activation.

“Now that we know this muscle–nerve crosstalk exists, it can be useful for treating things like nerve injury, where communication between nerve and muscle is cut off,” said Raman.

Looking ahead, the research team plans to explore targeted muscle stimulation further, focusing on its potential to promote nerve growth and regeneration in clinical settings. This work could shift the role of exercise in medicine, transforming it from a general health practice to a precise therapeutic tool for nerve repair.

“This is just our first step toward understanding and controlling exercise as medicine,” Raman concluded. 

Reference: Bu A, Afghah F, Castro N, et al. Actuating extracellular matrices decouple the mechanical and biochemical effects of muscle contraction on motor neurons. Adv Healthcare Materials. 2024:2403712. doi: 10.1002/adhm.202403712

This article is a rework of a press release issued by the Massachusetts Institute of Technology. Material has been edited for length and content.