Exercising regularly provides benefits that spread throughout the body, as it not only strengthens muscles, but also strengthens bones, blood vessels and the immune system. Physical activity has also been associated with a lower risk of developing neurodegenerative diseases, and a new study has shown that exercising your muscles has important benefits for neurons.
A team of engineers from the Massachusetts Institute of Technology (MIT) has proven that when muscles contract during exercise, a series of biochemical signals known as myokines are released, and when neurons are exposed to these signals generated by the muscles, they grow. four times more than those that are not in contact with myokines. These experiments at the cellular level suggest that exercise has a significant biochemical impact on nerve growth.
Surprisingly, the researchers also discovered that neurons not only respond to the biochemical signals of exercise, but also to its physical effects, as they observed that by repeatedly subjecting neurons to a stretch similar to the muscle contraction and expansion that occurs During exercise, these grow as much as when exposed to muscle myokines.
Although previous studies suggested a biochemical link between muscle activity and nerve growth, this research is the first to show that physical effects are equally important. The results have been published in the journal Advanced Healthcare Materials and provide information about the connection between muscles and nerves during exercise, which could contribute to the development of rehabilitation therapies to repair damaged or deteriorated nerves.
“Now that we know that there is this communication between muscle and nerve, this can be useful to treat nerve injuries, where the communication between the two is interrupted,” said Ritu Raman, assistant professor of Mechanical Engineering at MIT in a note published by the center. “Perhaps if we stimulate the muscle we could encourage the nerve to heal, and restore mobility to people who have lost it due to a traumatic injury or neurodegenerative diseases.”
Biochemical effects of exercise can promote neuronal growth
In 2023, Raman and his team managed to restore mobility in mice with traumatic muscle injuries, implanting muscle tissue in the injured area and then stimulating this tissue with light. Over time, they discovered that the grafted and exercised tissue helped the mice regain their motor function to reach activity levels comparable to those of healthy mice. Analysis of the graft showed that regular exercise stimulated the muscle to produce certain biochemical signals that promote the growth of nerves and blood vessels.
In their new study, the team focused exclusively on muscle and nerve tissues to determine whether muscle exercise has a direct effect on nerve growth. They grew mouse muscle cells into long fibers that fused together to form small muscle tissue. The team genetically modified this muscle so that it contracted in response to light, allowing the tissue to “exercise.”
“Perhaps if we stimulate the muscle we could encourage the nerve to heal, and restore mobility to people who have lost it due to a traumatic injury or neurodegenerative diseases.”
Raman developed an innovative gel mat to support and exercise muscle tissue, preventing it from coming loose during stimulation. They then collected samples of the surrounding solution, where they expected to find myokines, including growth factors, RNA, and other proteins. “Myokines are like a biochemical soup that muscles secrete, some of which can benefit the nerves,” Raman explained. “Muscles are always secreting myokines, but they produce more when exercising.”
The team transferred the solution with myokines to a plate with motor neurons, derived from mouse stem cells. After exposing them to the myokine mixture, they observed that the neurons grew four times faster than those that did not receive the biochemical solution.
To further study how neurons responded to myokines induced by exercise, they performed a genetic analysis that allowed them to observe that many genes related to neuronal growth and maturation were activated. The results suggest that the biochemical effects of exercise can promote neuronal growth. From there, the team asked whether the physical effects of exercise could have similar benefits.
To find out, they grew neurons on a gel mat with small magnets and then “exercised” them for 30 minutes daily using an external magnet to move the mat back and forth. Surprisingly, mechanical exercise stimulated neuronal growth as much as myokines. “It’s a good sign because it tells us that the biochemical and physical effects of exercise are equally important,” says Raman.
Now that they have shown that muscle exercise can promote nerve growth at a cellular level, they plan to study how targeted muscle stimulation could be used to heal damaged nerves and restore mobility to people with neurodegenerative diseases such as ALS. “This is just our first step in understanding and controlling exercise as medicine,” concludes Raman.
