When muscles work, they help nerve cells grow
By Jennifer Chu | MIT News Office | Published: 2024-11-20 18:00:00 | Source: Health – Big Think
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There is no doubt that exercise is good for the body. Regular activity not only strengthens muscles, it can strengthen bones, blood vessels, and the immune system.
Now, MIT engineers have discovered that exercise can also have benefits at the level of individual neurons. They observed that when muscles contract during exercise, they release a soup of biochemical signals called myokines. In the presence of these muscle-generated signals, the neurons grew four times farther than neurons that were not exposed to myokines. These experiments suggest at the cellular level that exercise can have a significant biochemical effect on nerve growth.
Surprisingly, the researchers also found that neurons respond not only to the biochemical signals of exercise, but also to its physical effects. The team observed that when neurons are repeatedly pulled back and forth, similar to how muscles contract and expand during exercise, neurons grow to the same extent as when they are exposed to muscle tension.
While previous studies have suggested a possible biochemical link between muscle activity and nerve growth, this study is the first to show that physical effects can be just as important, the researchers say. The results are Published today in the magazine Advanced healthcare materialshighlighted the relationship between muscles and nerves during exercise, and could benefit exercise-related therapies to repair damaged and degenerating nerves.
“Now that we know there’s this crosstalk between nerves and muscles, it could be useful in treating things like nerve injury, where the connection between nerves and muscles is broken,” says Ritu Raman, assistant professor of career development at Eugene Bell University at MIT. “Perhaps if we stimulate the muscle, we can encourage the nerve to heal, restoring mobility to those who have lost it due to traumatic injuries or neurodegenerative diseases.”
Raman is lead author of the new study, which includes Angel Poe, Firdaus Afgah, Nicolas Castro, Mahira Bawa, Sonika Kohli, Kareena Shah, and Brandon Rios of MIT’s Department of Mechanical Engineering, and Vincent Botti of MIT’s Koch Institute for Integrative Cancer Research.
Muscle talk
In 2023, Raman and her colleagues I mentioned They were able to restore mobility in mice that had suffered a traumatic muscle injury, by first transplanting muscle tissue at the site of the injury, then training the new tissue by repeatedly stimulating it with light. Over time, they found that exercise helped the mice regain their motor function, reaching activity levels similar to those found in healthy mice.
When the researchers analyzed the graft itself, it appeared that regular exercise stimulated the grafted muscles to produce certain biochemical signals known to promote nerve and blood vessel growth.
“That was interesting because we always think nerves control muscles, but we don’t think muscles talk to nerves,” Raman says. “So, we started to think that stimulating the muscle encourages nerve growth. And people responded that that might be the case, but there are hundreds of other cell types in the animal, and it’s really hard to prove that the nerve is growing more because of the muscle, rather than the immune system or anything else playing a role.”
In their new study, the team set out to determine whether exercising muscles has any direct effect on how nerves grow, by focusing solely on muscle and nerve tissue. The researchers grew mouse muscle cells into long fibers that then fused to form a small layer of mature muscle tissue about the size of a quarter.
The team genetically modified the muscles to contract in response to light. Through this modification, the team was able to flash a light repeatedly, causing the muscles to contract in response, in a way that mimics the action of exercise. Raman has previously developed a novel Gel mat That grows and exercises muscle tissue. The properties of the gel enable it to support muscle tissue and prevent it from peeling off while researchers stimulate the muscles for exercise.
Next, the team collected samples of the surrounding solution in which the muscle tissue had been exercised, believing that the solution must contain myokines, including growth factors, RNA, and a mixture of other proteins.
“I think myokines are a biochemical soup of things that muscles secrete, some of which may be good for the nerves and some of which may have nothing to do with the nerves,” Raman says. “Muscles always secrete myokines, but when you exercise them, they secrete more.”
“Exercise as medicine”
The team transferred the myokine solution to a separate dish containing motor neurons, which are nerves in the spinal cord that control muscles involved in voluntary movement. The researchers grew neurons from stem cells derived from mice. As with muscle tissue, neurons were cultured on a similar gel mat. After exposing the neurons to the myokine mixture, the team noticed that they began to grow rapidly, four times faster than the neurons that did not receive the biochemical solution.
“It grows much further and faster, and the effect is very immediate,” Raman says.
To take a closer look at how neurons change in response to exercise-induced myokines, the team performed a genetic analysis, extracting RNA from neurons to see if myokines caused any change in the expression of specific neuronal genes.
“We saw that many of the genes up-regulated in exercise-stimulated neurons were related not only to the growth of the neurons, but also to the maturity of the neurons, how well they communicate with muscles and other nerves, and how well their axons mature,” Raman says. “Exercise appears to affect not only the growth of nerve cells, but also how well they mature and function.”
The results suggest that the biochemical effects of exercise can promote nerve cell growth. The group then wondered: Could the purely physical effects of exercise have a similar benefit?
“Neurons are physically attached to the muscles, so they also stretch and move with the muscles,” Raman says. “We also wanted to see, even in the absence of biochemical signals from muscles, could we stretch neurons back and forth, simulating mechanical forces (exercise), and could that have an effect on growth as well?”
To answer this question, the researchers grew a different population of motor neurons on a gel mat that they embedded with small magnets. They then used an external magnet to move the mat and neurons back and forth. In this way, they exercised the neurons for 30 minutes a day. To their surprise, they found that this mechanical exercise stimulated the neurons to grow just like myokine-induced neurons, growing significantly further than neurons that had not received any form of exercise.
“This is a good sign because it tells us that the biochemical and physical effects of exercise are equally important,” Raman says.
Now that the group has shown that muscle exercise can promote nerve growth at the cellular level, they plan to study how targeted muscle stimulation can be used to grow and heal damaged nerves, restoring mobility to people with a neurodegenerative disease like amyotrophic lateral sclerosis.
“This is just our first step toward understanding and controlling exercise as medicine,” Raman says.
Republished with permission MIT News. Read Original article.
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