Chemical Signals from Exercise Boost Brain Health

Physical activity is commonly mentioned as a way to improve both physical and mental health. Researchers at the Beckman Institute for Advanced Science and Technology discovered that it may also directly boost brain health. They investigated how the chemical signals emitted by muscles during exercise enhance neuronal development in the brain.
Their findings were published in the journal Neuroscience.
When muscles contract during exercise, such as when lifting a heavy weight, a variety of chemicals are released into the bloodstream. These chemicals have the ability to travel to various regions of the body, including the brain. The researchers were particularly interested in how exercise could enhance the hippocampus, a portion of the brain.

“The hippocampus is a crucial area for learning and memory, and therefore cognitive health,” said Ki Yun Lee, a Ph.D. student in mechanical science and engineering at the University of Illinois Urbana-Champaign and the study’s lead author. Understanding how exercise benefits the hippocampus could therefore lead to exercise-based treatments for a variety of conditions including Alzheimer’s disease.

The researchers obtained tiny muscle cell samples from mice and cultured them on cell culture dishes in the lab to extract the chemicals generated by contracting muscles and test them on hippocampus neurons. When the muscle cells reached maturity, they began to contract independently, releasing chemical signals into the cell culture.

The researchers combined the culture with the mature muscle cells’ chemical signals with another culture containing hippocampus neurons and other support cells known as astrocytes. They investigated how exposure to these chemical signals affected hippocampal cells using a variety of methods, including immunofluorescent and calcium imaging to track cell growth and multi-electrode arrays to record neuronal electrical activity.

The outcomes were stunning. When hippocampus neurons were exposed to chemical signals from contracting muscle cells, they produced larger and more frequent electrical responses, indicating strong growth and health. Within a few days, the neurons began firing more synchronously, indicating that they were building a more mature network and mirroring the architecture of neurons in the brain.

However, the researchers were still puzzled as to how these chemical signals resulted in the growth and development of hippocampus neurons. They then focused on the role of astrocytes in moderating this relationship to learn more about the mechanism linking exercise to better brain health.

“Astrocytes are the first responders in the brain before the compounds from muscles reach the neurons,” Lee said. Perhaps, then, they played a role in helping neurons respond to these signals.

The researchers discovered that removing astrocytes from the cell cultures led the neurons to emit even more electrical signals, implying that without the astrocytes, the neurons continued to grow—possibly to an unacceptable size.

“Astrocytes play a critical role in mediating the effects of exercise,” Lee said. By regulating neuronal activity and preventing hyperexcitability of neurons, astrocytes contribute to the balance necessary for optimal brain function.

Understanding the molecular link between muscular contraction and hippocampus cell development and control is only the first step toward understanding how exercise improves brain health.

“Ultimately, our research may contribute to the development of more effective exercise regimens for cognitive disorders such as Alzheimer’s disease,” Lee said.

In addition to Lee, the team also included Beckman faculty members Justin Rhodes, a professor of psychology; and Taher Saif, a professor of mechanical science and engineering.

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