Exercise fuels neuron growth through muscle signals

Exercise is well known for its broad health benefits, from strengthening muscles and bones to supporting heart and immune health. Now, a team of engineers from MIT has uncovered a new benefit: exercise can directly promote neuron growth.

Led by MIT’s Ritu Raman, a recent study shows that contracting muscles release biochemical signals, or myokines, which significantly enhance neuron growth. 

When neurons were exposed to these muscle-generated signals, they grew four times farther than those without exposure. This discovery could pave the way for new therapies focused on nerve repair and regeneration.

Muscle-nerve communication

This study provides the first evidence that physical activity itself can stimulate neuron growth as effectively as biochemical signals from muscles. 

While prior research hinted at a connection between muscles and nerve growth, MIT’s study goes further, revealing the powerful role both biochemical and physical effects play. 

The research, published in Advanced Healthcare Materials, highlights the essential link between muscle and nerve health and could have applications for therapies aimed at restoring nerve function.

“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, an assistant professor of mechanical engineering at MIT. 

“Maybe 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.”

Muscles influence nerve growth

In previous work, Raman’s team helped restore mobility in mice with traumatic muscle injuries by implanting new muscle tissue at the site of the injury and then stimulating it with light. 

Over time, this exercised muscle tissue produced certain biochemicals that promoted blood vessel and nerve growth, restoring function in injured areas.

This finding suggested muscles could influence nerve growth, and it led Raman’s team to explore whether muscle-generated signals might directly support nerve growth.

To isolate muscle responses, they engineered mouse muscle tissue that would contract when exposed to light.

Using a special gel mat that supports muscle tissue without detachment, the team stimulated muscle contractions, allowing the tissue to release a blend of myokines – biochemical messengers including proteins and RNA.

“Muscles are pretty much always secreting myokines, but when you exercise them, they make more,” Raman explained. After collecting this solution, the team introduced it to motor neurons to observe how they might respond.

Biochemical signals and neuron growth

The team applied the myokine solution to motor neurons derived from mouse stem cells.

Observing their behavior, the experts found that the neurons quickly extended, growing four times faster and farther than those not exposed to myokines.

“They grow much farther and faster, and the effect is pretty immediate,” Raman said.

A closer genetic analysis of the neurons showed that the myokines stimulated genes not only related to growth but also to neuronal maturation and function.

“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,” Raman explained. 

“Exercise seems to impact not just neuron growth but also how mature and well-functioning they are.”

Physical movement alone promotes growth

The researchers next wondered if neurons could respond similarly to exercise’s mechanical impacts without biochemical cues. 

“Neurons are physically attached to muscles, so they are also stretching and moving with the muscle,” Raman said. 

Using a gel mat embedded with tiny magnets, the team simulated mechanical stretching on a different set of neurons, “exercising” them by gently moving the mat back and forth.

Remarkably, this mechanical stimulation resulted in neuron growth similar to that induced by myokines. The findings suggest that exercise’s physical impacts may directly encourage neuron growth. 

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

Implications for restoring mobility

This breakthrough in understanding how muscles influence neurons opens new therapeutic possibilities for nerve repair and neurodegenerative conditions. 

By using targeted muscle stimulation, researchers hope to develop treatments for conditions such as ALS and other neurodegenerative diseases that affect nerve function.

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

With growing evidence that exercise supports nerve health on multiple levels, researchers are now focused on exploring the potential for exercise-based therapies to restore function and mobility for those affected by nerve damage or degeneration. 

These findings highlight the powerful role exercise could play in future neurotherapeutic approaches.

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