Exercise not only strengthens muscles but also reshapes the brain. A study published on February 13 in Neuron, a journal of Cell Press, revealed that the lasting improvements in endurance gained through repeated training—such as running longer and faster—are associated with specific changes in brain activity, which in turn help enhance muscle and heart function.
"A lot of people say after they exercise they feel more alert, they feel clearer-headed," said study corresponding author J. Nicholas Betley of the University of Pennsylvania. "So we wanted to understand what happens in the brain after exercise and how these changes affect exercise outcomes."
To this end, Betley and his colleagues observed in experiments that after mice ran on a treadmill, brain activity increased, particularly in nerve cells located in their ventromedial hypothalamus (VMH). This brain region plays an important role in how the body utilizes energy, including regulating body weight and blood sugar.
By monitoring neural activity in mice, the research team discovered that a specific set of nerve cells in the VMH—called steroidogenic factor-1 (SF-1) neurons—became active when the mice ran. These neurons remained active for at least an hour after the mice stopped running.
After two weeks of daily training, the mice showed significant improvements in endurance, being able to run faster and longer before exhaustion. Correspondingly, the researchers found an increase in both the number and activity level of active SF-1 neurons in their brains compared to the beginning of the training period.
When the research team blocked the activity of SF-1 neurons, preventing them from sending signals to other parts of the brain, the animals tired quickly and showed no improvement in endurance during the two-week training period.
Surprisingly, even when SF-1 neurons functioned normally during exercise, blocking their activity immediately after exercise also hindered endurance improvement. This suggests that post-exercise SF-1 neuron activity is crucial for consolidating training effects and achieving endurance gains.
"When we lift weights, we think we're just training muscles," Betley said. "It turns out we may also be training our brains while we exercise."
Although the underlying mechanisms remain unclear, Betley suggests that active SF-1 neurons after exercise may help the body recover faster by utilizing stored glucose more efficiently. This, in turn, may help organs such as muscles, lungs, and heart adapt more quickly to higher-intensity training.
Betley hopes that this research could in the future not only help older adults or stroke patients maintain mobility but also assist athletes and young people recovering from injuries in enhancing their training outcomes.
"This study opens the door to understanding how to get the most out of exercise," he said. "If we can shorten the timeline and help people see results faster, it might encourage them to stick with their workouts."
Read the paper: https://www.cell.com/neuron/fulltext/S0896-6273(25)00989-4