Study reveals exercise stimulates neuron growth, paving way for new therapies in nerve repair

Regular exercise is widely acknowledged for its physical health benefits, which include muscle strength, cardiovascular fitness, and maintaining a healthy body weight.

However, a recent study by engineers at the Massachusetts Institute of Technology (MIT) discovered an exciting additional potential advantage of exercise: it may boost the growth of neurons, the cells responsible for signal transmission throughout the body.

The study, published in Advanced Healthcare Materials, focuses on how physical activity may influence nerve cell regeneration, providing hope for future treatments for neurodegenerative illnesses and nerve injury.

Understanding how exercise affects neuron growth could lead to novel therapeutics for nerve injury and disorders like amyotrophic lateral sclerosis (ALS).

Neurons serve a fundamental role in coordinating muscle activity and transmitting vital information.

This new insight builds on previous work by MIT researchers, such as a 2023 paper published in Biomaterials.

In that study, researchers led by Ritu Raman, an assistant professor of mechanical engineering at MIT, revealed that activating muscle tissue might cause the formation of nerves and blood arteries in mice with severe muscle damage.

During the examination of the graft, the researchers discovered that the grafted muscle had released biochemical signals that stimulated neuron and blood vessel growth.

However, Raman's team questioned whether stimulating muscles could, in turn, promote nerve growth—a hypothesis initially met with skepticism by the scientific community due to the complexity of biological environments.

Raman and colleagues conducted a novel study that focused primarily on muscle and nerve tissue, with the goal of determining if training muscles directly affected the way nerves formed.

The researchers used mouse muscle cells to make tiny muscle sheets that they then triggered to contract with light.

They next examined the fluid around the muscles for myokines, which are molecular signals generated by muscles during exercise and include growth hormones and proteins that may be advantageous to neurons.

Raman had previously developed a novel gel mat for muscle development and exercise.

While the researchers encouraged the muscle to exercise, they enabled the muscle tissue to maintain its shape and structure rather than peeling away.

The scientists then took samples of the fluids around the muscle, believing they would contain myokines such as growth hormones, RNA, and proteins.

Myokines, Raman explained, are a complex soup of proteins released by muscles, some of which may be beneficial to neurons.

"Myokines are secreted by muscles nearly all the time, but they produce more when you exercise them," she said.

The researchers transferred the myokine solution to a different dish containing motor neurons, which are nerves in the spinal cord that regulate muscles engaged in voluntary movement.

They grew neurons from mouse stem cells. Neurons were grown on a gel mat similar to that used for muscular tissue.

After the neurons were exposed to the myokine mixture, the scientists noticed that they began to grow rapidly, about four times quicker than neurons that did not get the biochemical solution.

The researchers also conducted a genetic analysis to learn more about the neural changes induced by exercise.

Initially, scientists extracted RNA from a tiny cluster of neurons. Cells first transcribe instructions for protein production from a gene to RNA.

They estimated the extent of genetic action in the formation of those instructions by measuring the level of gene transcription.

This enabled them to determine whether myokines had any effect on the activation of specific neuronal genes.

They discovered that several of the more actively expressed genes were involved in fundamental processes such as brain growth, maturation, neuronal connection (including with muscle cells), and axon growth.

The findings revealed that exercise not only stimulated neuronal growth but also improved neural maturity and functional capacities.

The team intended to see if the physiological response to exercise could predict neural function.

Muscle movement exerts mechanical stresses on the structure of neurons due to their physical interaction.

To see if these forces could also alter neuron growth, the researchers conducted mechanical stimulation studies that tracked neuron growth in the absence of myokines.

This time, the researchers cultivated another batch of motor neurons on a gel matrix that contained microscopic magnetic particles.

When an external magnetic field was introduced, the particles' movement mechanically stretched the neurons, simulating the conditions under which they may encounter mechanical stresses during exercise.

They ran this test for 30 minutes every day.

The researchers discovered that mechanical stimulation significantly increased neuronal growth: on average, mechanically exercised neurons grew at the same rate as those stimulated with myokines.

Both groups of exercised neurons expanded much more than a group of control neurons that received no exercise at all.

The findings have significant implications for the development of exercise-based nerve regeneration therapies, particularly in the context of nerve injuries and neurodegenerative disorders like amyotrophic lateral sclerosis (ALS).

Researchers could use the crosstalk between muscles and neurons to develop novel therapy options to boost nerve cell regeneration and mending by activating the muscles surrounding them.

The researchers said in their paper that their discovery has practical implications in developing novel approaches for treating nerve injuries in which the nerve and muscle tissue are no longer communicating properly.

The team intends to investigate the use of targeted muscle stimulation to regenerate and develop neurons in a clinical context, which could help redefine the role of exercise in medicine and general health promotion by providing precise therapeutic intervention for nerve regeneration.