Physical activity, often recommended for enhancing physical and mental well-being, can also have a direct positive impact on brain health.
The release of various compounds into the bloodstream occurs when muscles contract during exercise, such as when the biceps exert force to lift a heavy weight. These compounds have the ability to travel throughout the body, including the brain.
The researchers at The Beckman Institute for Advanced Science and Technology have focused their attention on exploring the potential benefits of exercise for a specific brain region known as the hippocampus.
“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.
In order to examine the specific chemicals released by contracting muscles and their impact on hippocampal neurons, the researchers obtained small muscle cell samples from mice. These muscle cells were then cultured in dishes within the laboratory, where they matured and naturally contracted, thereby releasing their chemical signals into the cell culture.
The research team introduced this culture, which now contained the chemical signals from mature muscle cells, to another culture comprising hippocampal neurons and supportive astrocyte cells. Multiple techniques, including immunofluorescent and calcium imaging to monitor cell growth, as well as multi-electrode arrays to record neuronal electrical activity, were employed to assess how exposure to these chemical signals influenced the hippocampal cells.
The findings were remarkable. The exposure to chemical signals from contracting muscle cells prompted the hippocampal neurons to generate larger and more frequent electrical signals, indicative of robust growth and enhanced health. Within a few days, the neurons began firing these electrical signals in a more synchronized manner, suggesting the formation of a more mature neural network resembling the organization observed in the brain.
However, the researchers still sought to uncover further insights into the pathway connecting exercise to improved brain health. Consequently, they directed their attention to examining the role of astrocytes in mediating this relationship.
“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 made an intriguing discovery when they eliminated astrocytes from the cell cultures, as this led to an even greater number of electrical signals being generated by the neurons. This observation indicated that without the presence of astrocytes, the neurons continued to grow, potentially reaching a point where their activity could become uncontrolled.
According to Lee, one of the researchers involved in the study, astrocytes play a crucial role in facilitating the effects of exercise. By regulating neuronal activity and preventing excessive excitability, astrocytes contribute to maintaining the necessary balance for optimal brain function.
Although understanding the chemical pathway connecting muscle contraction to the growth and regulation of hippocampal neurons is merely the initial step, it paves the way for comprehending how exercise can effectively enhance brain health.
Lee further expressed that their research might ultimately contribute to the development of more effective exercise routines specifically designed for cognitive disorders like Alzheimer’s disease.
The research team comprised not only Lee but also other esteemed members of the Beckman Institute, including Justin Rhodes, a psychology professor, and Taher Saif, a mechanical science and engineering professor.
Astrocyte-mediated Transduction of Muscle Fiber Contractions Synchronizes Hippocampal Neuronal Network Development
Exercise supports brain health in part by enhancing hippocampal function. The leading hypothesis is that muscles release factors when they contract (e.g., lactate, myokines, growth factors) that enter circulation and reach the brain where they enhance plasticity (e.g., increase neurogenesis and synaptogenesis). However, it remains unknown how the muscle signals are transduced by the hippocampal cells to modulate network activity and synaptic development.
Thus, we established an in vitro model in which the media from contracting primary muscle cells (CM) is applied to developing primary hippocampal cell cultures on a microelectrode array.
We found that the hippocampal neuronal network matures more rapidly (as indicated by synapse development and synchronous neuronal activity) when exposed to CM than regular media (RM).
This was accompanied by a 4.4- and 1.4-fold increase in the proliferation of astrocytes and neurons, respectively. Further, experiments established that factors released by astrocytes inhibit neuronal hyper-excitability induced by muscle media, and facilitate network development.
Results provide new insight into how exercise may support hippocampal function by regulating astrocyte proliferation and subsequent taming of neuronal activity into an integrated network.
“Astrocyte-mediated Transduction of Muscle Fiber Contractions Synchronizes Hippocampal Neuronal Network Development” by Ki Yun Lee et al. Neuroscience