Exercise improves brain health with chemical signals

Summary: Chemical signals released by muscles during exercise promote neural development in the brain, researchers report.

source: Beckman Institute

Physical activity is often cited as a means of improving 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 the development of neurons in the brain.

Their work appears in the magazine Neurology.

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

“The hippocampus is a key area for learning and memory, and therefore cognitive health,” said Kee Yoon Lee, Ph.D. student in mechanical science and engineering at the University of Illinois Urbana-Champaign and lead author of the study. Therefore, understanding how exercise benefits the hippocampus could 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 hippocampal neurons, the researchers collected small samples of muscle cells from mice and grew them in cell culture dishes in the lab. As muscle cells mature, they begin 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 from the mature muscle cells, to another culture containing hippocampal neurons and other supporting cells known as astrocytes.

Using several measures, including immunofluorescence and calcium imaging to track cell growth and multi-electrode arrays to record neuronal electrical activity, they investigated how exposure to these chemical signals affected hippocampal cells.

The results were astounding. Exposure to the chemical signals from the contracting muscle cells causes hippocampal neurons to generate larger and more frequent electrical signals—a sign of robust growth and health. Within a few days, the neurons began to fire these electrical signals more synchronously, suggesting that the neurons form a more mature network together and mimic the organization of neurons in the brain.

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

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

When muscles contract during exercise, such as the biceps working to lift a heavy weight, they release various compounds into the blood. Image is in the public domain

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

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

Understanding the chemical pathway between muscle contraction and the growth and regulation of hippocampal neurons is just the first step in understanding how exercise helps improve 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, professor of psychology; and Taher Saif, professor of mechanical sciences and engineering.

About this news about neuroscience and exercise research

Author: Melin Lai
source: Beckman Institute
Contact: Melin Lai-Beckman Institute
Image: Image is in the public domain

Original Research: Closed access.
“Astrocyte-mediated transduction of muscle fiber contractions synchronizes hippocampal neural network development” by Ki Yun Lee et al. Neurology


Astrocyte-mediated transduction of muscle fiber contractions synchronizes hippocampal neural network development

Exercise supports brain health in part by improving hippocampal function. The leading hypothesis is that muscles release factors when they contract (eg, lactate, myokines, growth factors) that enter the circulation and reach the brain, where they enhance plasticity (eg, increase neurogenesis and synaptogenesis). However, it remains unknown how muscle signals are transduced by hippocampal cells to modulate network activity and synaptic development.

That’s how we created an IVF model in which medium from contracting primary muscle cells (CM) is applied to grow primary hippocampal cell cultures on a microelectrode array.

We found that the hippocampal neural network matured faster (as indicated by synapse development and synchronous neuronal activity) when exposed to CM than regular medium (RM).

This was accompanied by a 4.4- and 1.4-fold increase in the proliferation of astrocytes and neurons, respectively. Additionally, the experiments found that factors released by astrocytes inhibited neuronal hyperexcitability induced by the muscle environment and facilitated network development.

The results provide new insight into how exercise can support hippocampal function by regulating astrocyte proliferation and subsequent taming of neuronal activity in an integrated network.

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