Exercise, the Brain and Endurance: a Central Nervous System Signal Identified in Mice

New findings indicate that the benefits of exercise would be far less pronounced without contributions from the brain. In a mouse study, researchers identified a key signal within the central nervous system that appears to help the rest of the body build physical endurance after repeated exercise sessions.

Moving beyond muscles: how the brain helps remodel the body for exercise

For many years, the prevailing view was that the body’s broad adaptations to frequent exercise happened largely in the periphery - in tissues such as bones and muscles, as well as the heart. A team of US researchers, led by scientists at the University of Pennsylvania, now argues that the brain plays a central part in reshaping the body for sustained physical activity.

Based on their work in mice, the team proposes that specific central nervous system signalling is “enhancing exercise endurance and coordinating peripheral metabolic adaptations”.

Ventromedial hypothalamus (VMH) activity rises after treadmill running

In the experiments, mice ran on a treadmill and, afterwards, researchers observed heightened activity in neurons located in the ventromedial hypothalamus (VMH). The VMH is recognised for its role in matching the body’s energy expenditure to its needs.

Among the VMH neurons, a particular group showed the strongest exercise-linked response: steroidogenic factor-1 (SF1) neurons. Their activity did not drop off immediately when running stopped; instead, it stayed elevated for at least an hour after the mice finished.

SF1 neurons, endurance and training effects over 3 weeks

After 3 weeks of training - with mice running 5 days a week - the animals were able to run longer and at higher speeds before becoming exhausted. Alongside this improved performance, signals from their SF1 neurons were higher than they had been at the start of the study.

Crucially, when the researchers blocked SF1 neuron activity in some mice, the usual endurance improvements did not occur. In contrast, artificially activating the SF1 neurons boosted endurance performance.

Taken together, these observations point to a strong role for SF1 neuron activity in governing how the body adapts to repeated exercise and in expanding endurance capacity.

“We might be building up our brain when we exercise”

“When we lift weights, we think we are just building muscle,” says biologist J. Nicholas Betley of the University of Pennsylvania. “It turns out we might be building up our brain when we exercise.”

A growing body of evidence suggests exercise does much more than develop muscle and reduce fat. Even brief, regular bouts of physical activity may improve brain function and could potentially make the central nervous system appear younger.

Although the effects of exercise on the brain are often discussed separately from its effects on the body, this research supports the view that the two are closely connected. Betley and colleagues add to the argument that exercise can bridge body and brain, and may offer a powerful avenue for treating mental health conditions such as depression.

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

How VMH neurons integrate insulin and glucose signals during exercise

Neurons in the brain’s VMH are known to combine information arriving from the body - including insulin and glucose levels - in order to regulate energy expenditure. The researchers report that without these neurons, mice are unable to access the right energy stores or properly remodel their skeletal-muscular systems during exercise.

Following repeated physical activity, VMH neurons in mice also displayed close to twice the density of dendritic spines. These finger-like structures receive messages from other brain cells. One possibility is that, by gathering more incoming information, these neurons may be better equipped to fine-tune the body’s energy balance during training and recovery.

What this might mean for people, and what still needs testing

Because these results come from mice, further research in humans is needed to find out whether VMH neurons in our own species undergo comparable changes after exercise. Studies in people could also help clarify whether different types of training (for example, endurance work versus resistance training) produce distinct central nervous system responses, and whether those patterns relate to improvements in fitness or mental wellbeing.

It will also be important to determine how long these brain changes persist, how they vary with age or baseline fitness, and whether they can be influenced by factors such as sleep and diet - all of which affect insulin, glucose and energy expenditure.

The study was published in Neuron.