A good workout doesn’t just boost your mood, it stimulates the brain’s ability to create new neurons. But how exactly this happens has puzzled researchers for years. “It’s been a bit of a black box,” says Tara Walker, a neuroscientist at the University of Queensland’s Brain Institute.
Now Walker and his colleagues believe they have found a key: the chemical element selenium. During exercise, mice produce a selenium-containing protein that helps their brains grow new neurons, the team reports today. Scientists may also be able to harness the element to help reverse cognitive decline due to old age and brain damage, according to the authors.
It’s a “fantastic” study, says Bárbara Cardoso, a nutritional biochemist at Monash University’s Victorian Heart Institute. His own research has shown that selenium, found in Brazil nuts, grains and some legumes,improves verbal fluency and the ability to correctly copy drawings in the elderly. “We could start thinking about selenium as a strategy” to treat or prevent cognitive decline in people who can’t exercise or who are more vulnerable to selenium deficiency, she says, such as older adults. and patients with stroke and Alzheimer’s disease.
In 1999, researchers reported that running stimulates the brain to make new neurons in the hippocampus, a region involved in learning and memory. But which molecules were released into the bloodstream to trigger this “neurogenesis” remained unclear.
So 7 years ago, Walker and his colleagues examined blood plasma of mice that had exercised on a running wheel in their cage for 4 days, compared to mice that did not have a wheel. The team identified 38 proteins whose levels increased after training.
One in particular caught Walker’s attention: selenoprotein P (SEPP1). This protein, which transports selenium to the brain and has antioxidant properties, more than doubled after rodent training.
In the new study, Walker’s team added one of two forms of selenium – sodium selenite (present as a salt in water and soil) or selenomethionine (present as an amino acid in food) – to a dish filled with cells that give rise to new neurons. In just 14 days, the number of these “neural precursor cells” doubled. When researchers injected sodium selenite directly into the brains of mice for 7 days, the number of neural precursor cells in the hippocampus tripledthey report in Cell metabolism.
“I’ve been working on neurogenesis for almost 20 years…and we’ve never seen anything like this before,” says Walker.
Mice genetically engineered to lack SEPP1 or its receptor did not receive an increase in neural precursor cells with exercise, the team found, confirming that SEPP1 was key to making new neurons.
“It is the first time that a substance that is usually found in food has been shown to have such a relevant and clear effect on neurogenesis,” explains Juan Encinas, neurobiologist at the Basque Neuroscience Center in Achucarro. But he says other blood proteins stimulated by exercise may also be involved.
To find out if selenium can help the aging brain, Walker’s team added selenomethionine to the drinking water of 18-month-old mice (the equivalent of 60-year-old humans). After nearly a month, the number of new neurons in the rodent hippocampus had doubled.
Selenium-treated mice also performed better than controls in two memory tasks that rely on this region of the brain. In the first, treated mice learned to avoid a spot where they received a mild electric shock better than controls. In the second, the team placed the mice in a brightly lit table with 32 holes, one of which allowed the animals to escape into a darkened room. (Mice instinctively avoid bright, open spaces.) Using the markings on the table as cues, the treated mice learned to escape about twice as fast as the controls.
Finally, the researchers investigated whether selenium could help reverse cognitive deficits resulting from brain injury. They injected a molecule into the hippocampus of mice to cause a stroke-like lesion that destroys neurons and damages memory. Damaged but treated mice performed as well as normal mice on a series of memory tasks. Untreated injured mice, on the other hand, did not recognize objects as new and had difficulty remembering where they had been shocked the day before.
The effects of recovery seemed to depend on stimulating neurogenesis: in a mouse model where scientists could “suppress” newly formed neurons, the beneficial effects of selenium disappeared.
The new findings are “another piece of the puzzle” of how exercise affects neurogenesis and cognition, says Sandrine Thuret, a neuroscientist at King’s College London who was not involved in the work. She notes that a recent study showed that clusterin, a molecule that also activates the SEPP1 receptor – LRP8 – is also high in the blood after physical activity in mice and humans, and stimulates memory. “It does that [new] even more exciting paper.
Selenium is an inexpensive and widely available supplement. But Cardoso warns that the chemical is toxic in high doses and that people who have normal selenium levels are less likely to benefit from supplementation. Still, she says, these preliminary results open avenues for testing selenium compounds to treat stroke patients. “I’m looking forward to future studies in humans to see if they find the same thing.”