Good exercise not only improves your mood, it also increases the brain’s ability to create new neurons. But exactly how this happens has baffled researchers for years. “It’s been a bit of a black box,” says Tara Walker, a neuroscientist at the University of Queensland Brain Institute.
Now Walker and his colleagues think they have found a clue: 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 harness the element to help reverse cognitive decline due to old age and brain injury, the authors say.
It’s a “fantastic” study, says Barbara Cardoso, a nutritional biochemist at Monash University’s Victorian Heart Institute. Her own research has shown that selenium, found in Brazil nuts, grains, and some legumes,improves verbal fluency and the ability to copy pictures correctly in older adults. “We could start thinking about selenium as a strategy” to treat or prevent cognitive decline in those who can’t exercise or are more vulnerable to selenium deficiency, he says, such as older adults and patients with stroke and disease. Alzheimer’s.
In 1999, researchers reported that running stimulates the brain to produce new neurons in the hippocampus, a region involved in learning and memory. But what molecules were released into the bloodstream to trigger this “neurogenesis” remained unclear.
So, 7 years ago, Walker and his colleagues analyzed blood plasma of mice that had exercised on a running wheel in their cages for 4 days, versus mice that did not have a wheel. The team identified 38 proteins whose levels increased after training.
One in particular caught Walker’s eye: selenoprotein P (SEPP1). This protein, which transports selenium to the brain and has antioxidant properties, more than doubled after the rodents exercised.
In the new study, Walker’s team added either of two forms of selenium — sodium selenite (found as salt in water and soil) or selenomethionine (found as an amino acid in the diet) — to a plate full of cells that give rise to new neurons. In just 14 days, the number of these “neural precursor cells” doubled. When the researchers injected sodium selenite directly into the brains of mice for 7 days, the number of neural precursor cells in the hippocampus tripledreport on Cellular 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 get a boost in neural precursor cells with exercise, the team found, confirming that SEPP1 was key to producing the new neurons.
“This is the first time that a substance normally present in the diet has such a relevant and clear effect on neurogenesis,” says Juan Encinas, a neurobiologist at the Achucarro Basque Center for Neurosciences. but he says other blood proteins exercise-enhanced may also be at play.
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 almost a month, the number of new neurons in the rodents’ hippocampus had doubled.
The selenium-treated mice also performed better than controls on two memory tasks that depend on this brain region. In the first, the treated mice learned to avoid a place where they received a mild electric shock better than the controls. In the second, the team placed the mice on a well-lit table with 32 holes, one of which allowed the animals to escape into a dark chamber. (Mice instinctively avoid bright, open spaces.) Using marks 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 that result from brain injury. They injected a molecule into the hippocampus of mice to cause a stroke-like injury that destroys neurons and impairs memory. The injured but treated mice performed as well as normal mice on a set 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 recovery effects seemed to be dependent on driving neurogenesis: In a mouse model in which scientists could “kill” newly formed neurons, the beneficial effects of selenium disappeared.
The new results 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 points out that a recent study showed that clusterin, a molecule that also activates the SEPP1 receptor LRP8, is also elevated in the blood after physical activity in mice and humans, and enhances memory. “That makes this [new] even more exciting role.
Selenium is a cheap and widely available supplement. But Cardoso cautions that the chemical is toxic in high doses and that people who have normal selenium levels are less likely to benefit from supplementation. Still, he 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.”
