Exercise trains a mouse's brain to build endurance

(Press-News.org) Exercise does more than strengthen muscles; it also rewires the brain. In a study publishing February 12 in the Cell Press journal Neuron, researchers reveal that the lasting gain in endurance from repeated exercise—such as the ability to run farther and faster over time—involves changes in brain activity that help muscles and hearts to become stronger.  

“A lot of people say they feel sharper and their minds are clearer after exercise,” says corresponding author J. Nicholas Betley of the University of Pennsylvania. “So we wanted to understand what happens in the brain after exercise and how those changes influence the effects of exercise.” 

In their experiments, Betley and his colleagues noticed that mice had increased brain activity after running on the treadmill, especially in the nerve cells located in their ventromedial hypothalamus (VMH). This brain region plays an important role in how the body uses energy, including regulating body weight and blood sugar. 

By monitoring neural activity in mice, the team found that a specific group of nerve cells in the VMH, called steroidogenic factor-1 (SF1) neurons, became active when the animals ran on a treadmill. These neurons also stayed active for at least an hour after the mice finished running.  

After daily exercise for two weeks, these mice showed improvement in endurance. They were able to run faster and longer before becoming exhausted. When researchers looked at the mice’s brains, they saw that more SF1 neurons in mice became active, and the activity levels were significantly higher than at the beginning of training.  

When the team blocked SF1 neuron activity and prevented them from sending signals to the rest of the brain, these animals got tired quickly and showed no improvements in endurance over the two-week training period.  

To the researchers’ surprise, blocking SF1 neurons only after exercise also prevented endurance gains even though the neurons functioned normally during exercise itself. This result suggests the important role for SF1 activity after exercise.  

“When we lift weights, we think we are just building muscle,” says Betley. “It turns out we might be building up our brain when we exercise.” 

While the underlying mechanism remains unclear, Betley says that active SF1 neurons post-exercise may help the body recover faster by using glucose stored in the body more efficiently. This may allow other parts of the body—like the muscle, lungs, and heart—to adapt more quickly to harder workouts. 

Betley hopes that this research could one day help older people or people recovering from stroke stay active while also benefiting athletes and younger people recovering from injury. 

“This study opens the door for understanding how we can get more out of exercise,” he says. “If we can shorten the timeline and help people see benefits sooner, it may encourage them to keep exercising.”  

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This work was supported by the University of Pennsylvania, the National Institutes of Health, the National Science Foundation, the National Research Foundation of Korea, the Rhode Island Institutional Development Award, the Rhode Island Foundation, and Providence College. 

Neuron, Betley et al., “Exercise induced activation of VMH SF1 neurons mediates improvements in endurance” https://www.cell.com/neuron/fulltext/S0896-6273(25)00989-4

Neuron (@NeuroCellPress), published by Cell Press, is a bimonthly journal that has established itself as one of the most influential and relied upon journals in the field of neuroscience and one of the premier intellectual forums of the neuroscience community. It publishes interdisciplinary articles that integrate biophysical, cellular, developmental, and molecular approaches with a systems approach to sensory, motor, and higher-order cognitive functions. Visit: http://www.cell.com/neuron. To receive Cell Press media alerts, contact press@cell.com. 

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