How exercise can help keep our memory sharp

Intriguing new study shows how exercise can boost brain health. The study involved mice, but found that a hormone produced by muscles during exercise can pass through the brain and improve the health and function of neurons, thereby improving thinking and memory in healthy animals and those with a rodent version of Alzheimer’s disease. Previous research has shown that people produce the same hormone during exercise, and together the findings suggest that movement may alter the trajectory of memory loss in aging and dementia.

We already have a lot of evidence that exercise is good for the brain. Studies in humans and animals show that exercise causes new neurons to be created in the brain’s memory center, then helps these new cells survive, mature, and integrate into the brain’s neural network. where they can help thinking and remembering. Large-scale epidemiological studies also indicate that active people tend to be much less likely to develop Alzheimer’s disease and other forms of dementia than people who exercise infrequently.

But how does training affect the inner workings of our brains at the molecular level? Scientists hypothesized that exercise could directly alter the biochemical environment inside the brain, without involving the muscles. Alternatively, muscles and other tissues can release substances during physical activity that travel to the brain and initiate processes there, leading to subsequent improvements in brain health. But in this case, the substances should be able to cross the protective and largely impermeable blood-brain barrier that separates our brains from the rest of our bodies.

These tangled questions were of particular interest ten years ago to a large group of scientists at Harvard Medical School and other institutions. In 2012, some of these researchers, led by Bruce M. Spiegelman, Stanley J. Korsmeyer Professor of Cell Biology and Medicine at the Dana-Farber Cancer Institute and Harvard Medical School, identified a previously unknown hormone produced in the muscles of laboratory rodents. and people during exercise, then released into the bloodstream. They named the new hormone irisin, after the messenger god Iris in Greek mythology.

Following the theft of irisin from the blood, they often found it in fatty tissue, where it was sucked in by fat cells, triggering a cascade of biochemical reactions that helped turn ordinary white fat into brown. Brown fat is much more metabolically active than much more common white fat. It burns a lot of calories. Thus, irisin, by helping to create brown fat, helps boost our metabolism.

But Dr Spiegelman and his colleagues suspected that irisin might play a role in brain health as well. A 2019 study by other researchers showed that irisin is produced in the brains of mice after exercise. This earlier research had also detected the hormone in most human brains donated to a large brain bank – unless the donors died of Alzheimer’s disease, in which case their brains contained virtually no irisin.

This study strongly suggested that irisin reduces the risk of dementia. And in the new study, published last week in Nature Metabolism, Dr Spiegelman and colleagues set out to quantify how.

They started by raising mice that were congenitally incapable of producing irisin, and then allowing those mice and other normal adult mice to run on wheels for a few days, which the animals seem to love to do. This form of exercise typically improves subsequent performance in rodent memory and learning tests, which have occurred in normal runners. But animals unable to make irisin showed little cognitive improvement, leading researchers to conclude that irisin is essential for exercise to improve thinking.

They then took a closer look at the brains of mice that ran with and without the ability to make irisin. All contained more newborn neurons than the brains of sedentary mice. But in animals without irisin, these new brain cells looked strange. They had fewer synapses, the junctions where brain cells send and receive signals, and dendrites, the winding tendrils that allow neurons to connect to the neural communication system. These newly formed neurons would not easily fit into the brain’s existing network, the researchers concluded.

But when scientists used chemicals to increase irisin levels in the blood of animals unable to make theirs, the situation in their brains changed dramatically. Young mice, elderly animals, and even those with advanced cases of Alzheimer’s disease in rodents began to perform better on tests of their memory and ability to learn. The researchers also found signs of reduced inflammation in the brains of animals with dementia, which is important because neuroinflammation is thought to accelerate the progression of memory loss.

Importantly, they also confirmed that irisin flows to and crosses the blood brain barrier. After the researchers injected the hormone into the blood of genetically engineered mice, it appeared in their brains, although their brains were unable to produce it.

Taken together, these new experiences strongly suggest that irisin is a key component in “linking exercise to cognition,” said Dr Spiegelman.

It could also someday be developed as a medicine. He said he and his collaborators, including Christiane D. Wrann, assistant professor at Massachusetts General Hospital and Harvard Medical School and lead author of the new study, hope to eventually test whether pharmaceutical versions of irisin could slow the decline. cognitive or even increase thinking skills in people with Alzheimer’s.

This was a mouse study, however, and a lot of research has yet to be done to determine whether our brain reacts like rodent’s to irisin. It’s also unclear how much or what types of exercise might best boost our irisin levels. But even now, says Dr Wrann, the study reinforces the idea that exercise may be “one of the most important regulators” of brain health.