MIT engineers have discovered that exercise benefits muscles and individual neurons. When muscles contract during exercise, they release biochemical signals called myokines, which stimulate neurons to grow four times farther than those not exposed to these signals.
Additionally, neurons respond to the physical impact of exercise—specifically, being stretched and pulled, similar to muscle movements—promoting growth just as effectively as the biochemical signals. This research suggests exercise has a significant biochemical and physical impact on nerve growth.
This study is the first to show that both biochemical signals and physical effects from exercise can promote nerve growth, revealing a crucial connection between muscles and nerves. The findings have potential therapeutic implications, particularly for treating nerve injuries or neurodegenerative diseases.
The Eugene Bell Career Development Assistant Professor of Mechanical Engineering at MIT, Ritu Raman, said, “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. If we stimulate the muscle, we could encourage the nerve to heal and restore mobility to those who have lost it due to traumatic injury or neurodegenerative diseases.”
Having demonstrated that exercising muscle can promote nerve growth at the cellular level, the team plans to investigate how targeted muscle stimulation might be used to heal damaged nerves.
Credits:Credit: Angel Bu
Their goal is to explore how this approach could restore mobility in people living with neurodegenerative diseases like ALS, which disrupt nerve-muscle communication. This research could pave the way for new therapies to repair nerve damage and improve motor function.
In 2023, Ritu Raman and her team showed that they could restore mobility in mice with traumatic muscle injuries by implanting and stimulating muscle tissue with light. Over time, the grafted muscle helped the mice regain motor function, reaching levels similar to healthy mice.
They discovered that exercise stimulated the grafted muscle to produce biochemical signals that promote nerve and blood vessel growth.
Initially, Raman and her team wondered whether other factors, like the immune system, were overshadowing the muscle’s influence on nerve growth. They focused their new study on muscle and nerve tissue alone to test this. They grew mouse muscle cells into long fibers, which fused into a sheet of mature muscle tissue, to investigate the direct impact of exercise on nerve growth.
The team genetically modified the muscle tissue to contract in response to light, allowing them to repeatedly mimic exercise by flashing light to stimulate the muscle. Raman had previously developed a special gel mat to support the muscle tissue during this process, preventing it from peeling away as it was exercised.
After stimulating the muscle, the researchers collected samples of the surrounding solution, expecting it to contain myokines—biochemical signals like growth factors, RNA, and proteins that could promote nerve growth.
The team transferred the myokine solution from the exercised muscle tissue to a separate dish containing motor neurons grown from mouse stem cells. After being exposed to the myokine mixture, the neurons grew four times faster and farther than those that did not receive the solution. Raman noted that the growth was both rapid and significant.
To investigate further, the researchers conducted a genetic analysis, extracting RNA from the neurons to examine whether the myokines triggered changes in the expression of specific neuronal genes, shedding light on the biochemical effects driving this enhanced growth.
Raman says, “We saw that many of the genes up-regulated in the exercise-stimulated neurons was 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 neuron growth and how mature and well-functioning they are.”
The researchers then wondered if the physical impacts of exercise—rather than just the biochemical signals—could also promote neuron growth. Since neurons are physically connected to muscles and stretch as muscles move, they hypothesized that mimicking these mechanical forces might similarly affect neurons.
To test this, they grew motor neurons on a gel mat embedded with tiny magnets. They then used an external magnet to jiggle the mat, simulating the stretching and movement of muscles during exercise.
They “exercised” the neurons for 30 minutes a day. Surprisingly, they found that this mechanical stimulation caused the neurons to grow as much as those exposed to myokines, growing significantly farther than neurons without exercise.
Raman said, “That’s a good sign because it tells us both biochemical and physical effects of exercise are equally important.”
Journal Reference:
- Angel Bu, Ferdows Afghah, Nicolas Castro, Maheera Bawa, Sonika Kohli, Karina Shah, Brandon Rios, Vincent Butty, Ritu Raman. Actuating Extracellular Matrices Decouple the Mechanical and Biochemical Effects of Muscle Contraction on Motor Neurons. Advanced Healthcare Materials. DOI: 10.1002/adhm.202403712
