Endurance brain cells may determine how long you can run for
Your Limits When Exercising Might Really Be All In Your Head
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Researchers have identified neurons in mice that help develop endurance after running. They suspect that there are similar cells in humans, which could be targeted by drugs or other therapies to amplify the effects of exercise.
We have known for decades that the brain changes with physical activity. Yet scientists generally thought these effects were distinct from those that occur elsewhere in the body, such as strengthening muscles, says Nicholas Betley of the University of Pennsylvania. The latest findings suggest otherwise: Brain changes “are what coordinate all these other things,” he says.
To better understand how exercise influences the brain, Betley and colleagues monitored neuronal activity in mice before, during and after treadmill exercise. They focused on cells in the ventromedial hypothalamus because previous research has shown that impaired development in this region of the brain hinders improved fitness in rodents. The same is likely true in humans, because the region’s structure and function tend to be consistent across mammals, Betley says.
The team found that after the mice ran, activity increased in a group of neurons with a receptor called SF1, which plays a role in brain development and metabolism. Additionally, the proportion of these cells activated by exercise increased with each additional day of running. By the eighth day, running activated about 53 percent of the neurons, compared to less than 32 percent on the first day. “So just as your muscles grow when you exercise them, your brain activity grows,” says Betley.
Next, the researchers used optogenetics – a technique that activates or inhibits neuronal activity with light – to deactivate these neurons in a separate group of mice. The animals trained on a treadmill five days a week for three weeks. After each session, the neurons were inhibited for one hour. At the end of each week, the mice performed an endurance test, running until they were exhausted.
Over the course of the experiment, the mice increased the distance traveled during these tests by about 400 meters on average, but that was about half the improvement seen in another group of mice whose neurons remained intact.
The role of these neurons is unclear, but it could be related to fuel use, says team member Morgan Kindel, also at the University of Pennsylvania. During endurance activities, the body fuels itself with fat because carbohydrate stores are depleted more quickly. But inhibiting these neurons in the mice caused them to “start using carbohydrates much earlier in the race,” Kindel says. “Then they kind of run out of fuel.” The team found that inhibiting these neurons prevents the release of a protein called PGC-1 alpha in muscles, which helps cells use fuel more efficiently. These neurons also release a substance that increases blood sugar and replenishes energy stores, thereby promoting muscle recovery.
Optogenetics requires invasive brain surgery and is therefore not feasible in humans. But it might be possible to develop other interventions that could act on these neurons, Betley says. “I really think if we could find a way – a salt, a supplement – to activate these neurons, we could increase endurance,” says Betley.
When the researchers repeated the experiment, stimulating rather than inhibiting the activity of these neurons, they found that the mice developed Herculean endurance, traveling more than twice the distance of control mice.
A similar intervention could particularly benefit people who have difficulty exercising, such as the elderly or those who have suffered a stroke, Betley says.
But there are many obstacles on the way. On the one hand, we don’t know for sure whether these results trickle down to people. There is also the question of potential side effects, explains Thomas Burris of the University of Florida. These neurons appear to regulate energy use in muscles, so stimulating them too much could cause a dangerous drop in blood sugar, he says.
Even if we can safely activate these neurons in humans, it won’t be a silver bullet for good health, Betley says. “All sorts of great things happen when you exercise: You’re less depressed, less anxious. There are cognitive, cardiovascular and muscular improvements,” he says. “I don’t think activation [these] neurons will necessarily be the bottleneck through which all these good things happen.
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