Research shows why exercise is good for the brain | National Geographic

How do muscles affect the brain?

During exercise, molecules that have a direct effect on brain aging are secreted. Research into this process only began 25 years ago with the publication of two studies by Henriette van Praag, a postdoctoral researcher at the Salk Institute for Biological Studies in California. In the research papers, van Praag described her research in the brains of adult mice that spent a lot of time on a treadmill and mice that didn’t. The results showed for the first time that mammals given enough exercise made many new neurons, a process called neurogenesis. The changes observed were accompanied by improvements in spatial memory and learning processes.

According to Van Praag, now an assistant professor at Florida Atlantic University’s Stiles-Nicholson Brain Institute, her discovery was partly the result of chance. In an earlier study, scientists had seen evidence that mice exposed to a “rich” environment (where they were given more and different stimuli, such as hiding places and games) made more new neurons. Van Praag wanted to know what was the critical factor in these mice. “Running on the treadmill was just a checkpoint in that study,” she laughs.

Van Praag’s work pioneered establishing a link between neurogenesis and improved cognitive function. Not only is this very important for neuroscience, but it has also paved the way for exercise researchers and muscularists who study the interaction between exercise, muscles, and the brain,” says Handchen.

In 2002, Bruce Spiegelman, a cell biologist at the Dana-Farber Cancer Institute and Harvard Medical School, was examining a protein called “PGC-1α,” which regulates the body’s metabolism by turning on and off certain genes. Spiegelman found that in mice given more of this protein, muscles became stronger, redder, and better veins. It was as if the rodents had trained so hard without ever putting a single foot on the treadmill.

At about the same time, scientists began to realize that moving muscles release a variety of hormones and other molecules called myokines into the bloodstream, and then these substances could be useful in all kinds of organs. In his research on the PGC-1α protein, Spiegelman asked himself the following question: If the muscles are reminiscent of muscles that have been heavily trained thanks to this protein, then PGC-1α may stimulate the muscles to release substances released during exercise. Will it be created?’ Use protein to find the molecules responsible for the positive changes in the metabolism and immune response caused by exercise.

The search for these molecules bore fruit in 2012, when Spiegelman and colleagues discovered irisin, a myocinogen secreted by moving muscles. The researchers were able to prove that the iris is able to convert white adipose tissue into brown adipose tissue. Since brown adipose tissue burns calories (while white adipose tissue stores calories), Spiegelman suggested that irisin may be key to being able to fight obesity and diabetes through exercise.

More puzzle pieces were put into place the following year, when Christian Rahn, a postdoctoral researcher at the time working with Spiegelmann, explained that muscles “talked” to the brain during exercise. When muscle cells produce irisin, it boosts production of another protein called “brain-derived neurotrophic factor” (BDNF) in the hippocampus, one of the first areas of the brain to undergo changes in neurodegenerative disorders.

In the hippocampus, BDNF promotes the health and growth of synapses and neurons, causes these cells to reach maturity, and improves synaptic plasticity in the organ.

Last year, Wrann, now a neurologist at Massachusetts General Hospital and Harvard Medical School, tested the role of irisin in exercise and cognitive function. Her team compared mice that were genetically modified and therefore unable to produce irisin with mice in the control group that made the molecule. Mice in the control group were better at performing spatial memory and learning tasks after a period of exercise than rats that were unable to produce irisin, suggesting that irisin is the substance that enhances these cognitive skills.

When Wrann’s team examined the rodents’ brains closely, they found that both groups of mice created new neurons in response to exercise, but the neurons in mice without irisin were abnormal: they were unable to make the usual connections. When the researchers reintroduced the gene responsible for producing irisin into the brains of mice that did not have irisin, these mice were able to distinguish two similar patterns more easily — a skill that people use, for example, when they park their car in a parking lot.

Neurological diseases

Wrann’s team also found that irisin likely plays a role in protecting against neurodegenerative disorders. The researchers bred mice that could not produce irisin and at the same time already had symptoms of Alzheimer’s disease. Mice with this double disability developed neurodegenerative symptoms more quickly than mice with Alzheimer’s disease only. In addition, they showed signs of cognitive improvement after restoring their iris production.

Wrann suspects that one of the ways irisin has benefited these animals is that it counteracts inflammatory responses caused by a malfunction in the brain’s immune system. This system consists mainly of so-called microglia and astrocytes. These glial cells normally suppress inflammation in the brain and remove waste after injury. But as mammals age, these cells can remain active after acute danger has passed, disrupting nerve function in the brain — first by destroying connections between neurons and then turning off the neurons themselves.

This activity triggers chronic inflammation in the brain associated with several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. But lab mice treated with irisin had less inflammation in the hippocampus, while the number of microglia and astrocytes also decreased in this region, suggesting that irisin helped control weakened immune defenses.

Could these findings also apply to humans? Preliminary research from Wrann’s lab and other teams may emerge. She says that irisin has an identical molecular structure in mice and humans, indicating that it plays the same role in both species.

The implications of this research are promising, as it shows that people have elevated levels of irisin in their blood after fitness training. Analyzes of brain tissue from deceased Alzheimer’s patients show that their brain tissue contains 70 percent less iris precursor molecule, compared to individuals of the same age. This suggests that irisin protects against neurodegenerative disorders.

From a clinical perspective, Handchen says, “irisin certainly shows promise, especially given the findings regarding how this compound works in the brain.” But he remains cautious: Irisin has not yet been exposed to the long line of gloves he will have to put up with on his way to a potential application as a drug. “It is not yet possible to determine if irisin can eventually be used in human patients.”

Depression and mood swings

Handschen is personally interested in the interactions between muscles, exercise, mood, and motivation. For an as-yet-unpublished study, his group investigated the effect of certain molecules released by muscle movements. Their research shows that mice that can’t make these molecules don’t feel the need to start running on a treadmill when they can — a behavior unusual in mice, as rodents typically run nearly six miles a day.

“There must be something going on in the muscles of these mice that somehow pushes this urge — to go jogging for pleasure — away,” Handchen says.

The promising potential of new treatments for mood disorders — particularly major depression — is what also interests Spiegelmann. It is considered that these cases are among the least treated disorders in medicine. “Severe depression is the leading cause of suicide and is especially common among young people,” he says. He and colleagues are currently evaluating the effect of irisin on depression in a lab study in mice.

Activities in the brain during body movements are not limited to “talking” to muscles. The interaction of all kinds of molecules — primarily proteins — secreted by the liver, fatty tissue and bone marrow — allows the brain to think in a more focused way. It also prevents depression and other disorders.

With scientists on the trail of promising drug candidates like Irisin and others, Curtis Rodriguez of the University of Alabama believes “we are on the brink of a great era of discoveries and discoveries finally translating into clinical practice.”

But Karina Alvinia, assistant professor of neurology at the University of Florida College of Medicine, cautions that the explosive growth of research into muscle-brain interactions is fraught with consequences and problems. The molecules involved have countless different effects on multiple systems, which means that while their potential is enormous, deciphering all of these interactions is a complex task. According to her, designing a drug without unintended side effects will still be a major challenge.

However, Alvinia looks forward to research that she does in confidence with others. This research shows that “the environmental and lifestyle choices we make can have a significant impact on the way we age,” she says. Therefore, it is partly up to us to age in a healthy way and maintain a higher quality of life into an advanced age.

“If there’s anything I can say about that, it’s that we need to stay active, even if you’re just walking for a few minutes a day. If you’re able to, you should definitely do it.”

This article was originally published in English at

Leave a Comment