Researchers have pinpointed specific neurons in mice that play a critical role in building endurance after physical activity. This discovery suggests that analogous cells may exist in humans, potentially offering new targets for pharmaceutical or therapeutic interventions aimed at enhancing the benefits of exercise.
For decades, it has been understood that the brain undergoes changes in response to physical exertion. However, a prevailing scientific view held that these neural effects were distinct from systemic physiological adaptations, such as muscle strengthening. New findings are challenging this perspective, indicating that brain changes are, in fact, integral to coordinating these other bodily responses to exercise.
Investigating Neural Activity During Exercise
To gain a deeper understanding of how exercise influences the brain, scientists observed neuronal activity in mice before, during, and after treadmill running. Their focus was directed towards cells within the ventromedial hypothalamus. Prior research had already established that compromised development in this brain region impedes fitness improvements in rodents. This region’s conserved structure and function across mammalian species suggest similar implications for humans.
Increased Neuron Activation with Training
The study revealed that following running sessions, a particular group of neurons, distinguished by the presence of the SF1 receptor, exhibited heightened activity. These neurons are known to be involved in brain development and metabolism. Notably, the proportion of these SF1-receptor-expressing neurons activated by exercise increased progressively with each consecutive day of running. After eight days of training, approximately 53 percent of these neurons were engaged, a significant increase from the less than 32 percent activated on the first day. This pattern suggests a growth in brain activity corresponding to increased exercise, analogous to muscle development through training.
Experimental Inhibition of Neuronal Activity
Subsequently, the researchers employed optogenetics, a technique using light to control neuronal activity, to deactivate these identified neurons for approximately one hour in a separate cohort of mice. This intervention was performed immediately after the mice completed a training regimen of treadmill running five days a week for three weeks. At the conclusion of each week, the mice underwent an endurance test, running until exhaustion.
During the experimental period, the mice in the inhibited group improved their running distance on these tests by an average of about 400 meters. However, this improvement was roughly half that observed in a control group of mice whose neurons remained unaffected.
Potential Role in Fuel Utilization
While the precise function of these neurons remains under investigation, it is hypothesized that their role is linked to fuel utilization during endurance activities. During prolonged exercise, the body primarily relies on fat for energy as carbohydrate stores deplete more rapidly. Inhibiting these neurons appeared to prompt the mice to “start using carbs a lot earlier on in the run,” leading to an earlier depletion of energy reserves and thus reduced endurance.
The team discovered that inhibiting these neurons prevents the release of PGC-1, a protein in muscles crucial for efficient fuel usage. Furthermore, these neurons secrete a substance that elevates blood sugar levels and replenishes energy stores, thereby supporting muscle recovery.
Therapeutic Possibilities and Challenges
Optogenetics, due to its invasive nature involving brain surgery, is not a practical approach for human application. However, the researchers believe that alternative interventions targeting these neurons could be developed. Activating these specific neurons through compounds like salts or supplements might offer a method to boost endurance, according to one of the lead researchers.
When the experiment was repeated, but this time enhancing, rather than inhibiting, neuronal activity, the results were striking. The mice exhibited significantly increased endurance, running more than double the distance of the control group.
Such interventions could prove particularly beneficial for individuals facing challenges with exercise, including older adults or those recovering from strokes.
However, several obstacles remain. The direct translation of these findings from mice to humans is not yet confirmed. Additionally, potential side effects require careful consideration. Over-stimulation of these neurons, which appear to regulate muscle energy uptake, could theoretically lead to a dangerous drop in blood sugar levels.
Even if safe methods for neuron activation in humans are developed, it is unlikely to be a singular solution for overall health. Exercise encompasses a broad spectrum of benefits, including improvements in mood, cognitive function, cardiovascular health, and muscle strength. Activating these particular neurons may not necessarily be the sole or primary bottleneck through which all these positive outcomes are achieved.