Exercise improves brain health through chemical signals, study finds

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Hippocampal neurons (yellow) surrounded by astrocytes (green) in a study cell culture. Image provided by the authors. Credit: Taher Saif, Justin Rhodes and Ki Yun Lee

Physical activity is frequently cited as a way to improve physical and mental health. Researchers at the Beckman Institute for Advanced Science and Technology have shown that it can also improve brain health more directly. They studied how chemical signals released by exercising muscles promote neuronal development in the brain.

Their work appears in the journal Neuroscience.

When muscles contract during exercise, such as the biceps working to lift a heavy weight, they release a variety of compounds into the bloodstream. These compounds can travel to different parts of the body, including the brain. The researchers were particularly interested in how exercise could benefit a particular part of the brain called the hippocampus.

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

To isolate the chemicals released by muscle contraction and test them on neurons in the hippocampus, the researchers collected small samples of mouse muscle cells and grew them in cell culture dishes in the lab. As the muscle cells matured, they began to contract on their own, releasing their chemical signals into the cell culture.

The research team added the culture, which now contained the chemical signals of mature muscle cells, to another culture containing hippocampal neurons and other supporting cells called astrocytes. Using multiple measures, including immunofluorescent and calcium imaging to track cell growth and multi-electrode arrays to record neuronal electrical activity, they examined how exposure to these chemical signals affected cells in the hippocampus. .

The results were startling. Exposure to chemical signals from contracting muscle cells caused neurons in the hippocampus to generate larger and more frequent electrical signals, a sign of robust growth and health. Within days, the neurons began to emit these electrical signals more synchronously, suggesting that the neurons together formed a more mature network and mimicked the organization of neurons in the brain.

However, researchers still had questions about how these chemical signals lead to the growth and development of hippocampal neurons. To further uncover the pathway linking exercise to better brain health, they then focused on the role of astrocytes in mediating this relationship.

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

The researchers found that removing astrocytes from cell cultures caused the neurons to emit even more electrical signals, suggesting that without the astrocytes, the neurons continued to grow, perhaps to a point where they could become unmanageable.

“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 chemical pathway between muscle contraction and hippocampal neuron growth and regulation is just the first step to understanding how exercise helps improve brain health.

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

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

More information:
Ki Yun Lee et al, Astrocytes-mediated transduction of muscle fiber contractions synchronizes hippocampal neural network development, Neuroscience (2023). DOI: 10.1016/j.neuroscience.2023.01.028

Journal information:

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