Muscle Workouts Stimulate Nerve Growth, Mice Study Finds

Exercise stimulates nerve growth and repair through both chemical signals and physical forces generated by muscle contractions.

MIT scientists find that motor neuron growth increased significantly over 5 days in response to biochemical (Left) and mechanical (Right) signals related to exercise. The green ball represents cluster of neurons that grow outward in long tails, or axons. Angel Bu

Contracting and exercising muscles may help nerves recover and grow after nerve damage, a new animal study has found.

During workouts, muscles release chemicals called myokines. Researchers at the Massachusetts Institute of Technology (MIT) found that motor neurons exposed to myokines grew four times more than those not exposed. Stretching the nerves to mimic the physical force of muscle contraction led to comparable growth results.

Motor neurons are nerves that help the body move. They differ from sensory neurons, which detect stimuli from the environment, and cortical neurons, responsible for cognition.

The researchers said the study’s findings may be promising for neurodegenerative diseases that affect motor neurons, such as amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

“Our hope is to be able to use this muscle-to-nerve signaling to promote nerve regrowth after injury or neurodegenerative diseases, but we have yet to show this effect works in diseased tissues, as our current study only focuses on healthy tissues,” Ritu Raman, the study’s senior author and an assistant professor of mechanical engineering at MIT, told The Epoch Times in an email.

Exercise-Triggered Muscle Chemicals Boost Neuron Growth

Nerves are known to control muscles, and recent research shows that muscles also affect nerve health through exercise, particularly the peripheral nerves—those outside the brain and spinal cord.

Myokines are molecules that communicate with cells and tissues throughout the body, influencing various biological processes. Although muscles primarily produce myokines during exercise, other cells also release these molecules during physical activity.

The new study, published on Nov. 10 in Advanced Healthcare Materials, takes a closer look at how exercise promotes nerve growth. Researchers grew genetically modified mouse muscles that contract when exposed to light. The muscles were placed on a gel-like mat and “exercised” for 30 minutes daily over five days. The researchers collected the solution surrounding the exercised muscles—believed to contain myokines and other secretions—and applied it to neurons.

Neurons exposed to the “exercise” solution showed significant increases across all measures of nerve growth: They grew more than four times longer, had single projections that grew 1.5 times farther, and covered 2.9 times more area than controls.

Some lab-grown muscles also twitched spontaneously, a common behavior in muscle cultures. Researchers found that myokines from these twitching muscles also promoted neuron growth, though the exercised-muscle solution had a more substantial effect. This suggests that more intense muscle activity promotes greater neuron growth.

The new study built on the team’s previous research. In 2023, the researchers made a breakthrough in understanding muscle–nerve communication. Using a lab-engineered muscle graft in mice with limb injuries, they demonstrated that muscle contractions alone promoted new nerve and blood vessel growth, restoring full mobility within two weeks. This finding suggested that muscle activity plays a crucial role in forming new nerve connections.

Further analysis revealed that repeated muscle contractions, similar to exercise, activated cellular signals that helped nerves grow, find their targets, and connect with muscles.

Stretching Neurons in the Absence of Myokines

The researchers also investigated the effect of physical force during exercise on nerves because the nerves also move with each muscle contraction, as they’re physically attached to the muscles.

They grew another set of neurons and used the same gel mat, embedded with tiny magnets and activated by a magnet outside to wobble the gel back and forth. This vibrated the mat, simulating the force the neurons would experience during actual muscle contraction. They exercised the nerves 30 minutes a day for five days.

Like nerves exposed to myokines, mechanically stimulated nerves showed significant increases across all growth measures: They grew nearly three times longer, with single projections extending 1.5 times farther, and covered three times more area than the controls.

However, while both types of stimulation helped neurons grow, only biochemical signals caused strong changes at the genetic level. Specifically, neurons exposed to myokines showed increased gene activity related to nerve growth and maturation, enhancing their ability to connect with other nerves and muscles.

Implications and Future Directions

There may be differences in the molecules released between mouse-derived tissues and human tissues, the researchers noted, suggesting that future studies should compare these differences to improve understanding.

“Our study is in vitro using mouse cell lines,” Raman said, adding that the team is currently adapting the mouse model to use human cells instead.

She said they’re “studying whether muscle-to-nerve signaling can be used to promote nerve regeneration after traumatic injury or diseases like ALS.”

“If our findings are translated to human models, therapeutic muscle stimulation would likely be accomplished by implanting electrodes directly in muscle tissue,” Raman added.

Nerve growth and healing are essential in treating conditions ranging from trauma-induced nerve damage to peripheral neuropathies caused by chemotherapy or metabolic issues, Michael Masi, a sports doctor and certified personal trainer at Garage Gym Reviews, who wasn’t part of the study, told The Epoch Times.

In line with the study’s findings, he noted that contracting muscles through their full range stimulates both biochemical and mechanical pathways supporting nerve repair. However, he cautioned, this type of exercise isn’t always suitable, especially in the acute stages of healing when inflammation is present or when the nerve is severely disrupted.

In such cases, he recommends two approaches: indirect healing through exercise of unaffected limbs, which stimulates the body’s natural healing processes without stressing the injured area, or gentle, targeted exercises for the injured area.

Masi said that the study suggests an “exocrine effect” from the release of myokines to promote healing at the nerves. Exocrine effects involve substances released to assist the organ from which they originate.

When asked about the possibility of creating a supplement or drug to mimic the effects of exercise-secreted myokines, Raman said that synthesizing myokines directly and using them as therapeutics could become an option if their composition is identified. This development could open new avenues for treating nerve injuries without relying solely on exercise-based therapies.

The study’s findings reinforce our understanding of the positive effects muscle contractions can have on nerve health, Gavin Williams, a UK-based neurological physiotherapist not involved in the study, told The Epoch Times.

“In the long term, these insights could have valuable implications for neurology and for physical and occupational therapy approaches in treating neurological conditions,” he said.