Selenium Supports New Neuron Growth and Mediates Brain Boost From Aerobic Exercise
Scientists once thought that neurogenesis — the creation of new neurons — ceases after the first few years of life. However, research has expanded in the last few decades to show that the creation of new brain cells can extend into adulthood, providing exciting new pathways for supporting cognition, learning, and memory in the aging or diseased brain. One proven way to boost neurogenesis is through exercise — but it’s not entirely understood why.
Now, researchers out of the University of Queensland Brain Institute in Australia propose that exercise-induced neurogenesis is mediated by releasing a protein that transports the mineral selenium. In a recent study published in Cell Metabolism, Leiter and colleagues show how exercising mice produce more of this selenium-shuttling protein that encourages new neuron growth, and with it, supports memory and learning even amongst the oldest mice. Further, the Australia-based team reports that dietary selenium supplementation can mimic the beneficial effects of exercise on neurogenesis, which could set the stage for the therapeutic use of this readily available mineral in supporting cognitive function in aging adults.
Nurturing New Neurons
A brain with higher levels of neurogenesis can better repair itself after injury or damage, leading to better cognitive function and neuroplasticity — the brain’s ability to adapt and change its structure and rewire connections. Neurogenesis also allows the brain to acquire new skills, improve emotional control and memory consolidation, and continually enhance cognitive ability.
The previously held belief that adults cannot form new brain cells originated from the notion that mature neurons cannot undergo cell division, meaning that cells in the nervous system do not regenerate like other cells in the body.
However, researchers have found that adult neurogenesis does occur — not through the cellular division of mature neurons, but, instead, via the differentiation (maturation) and self-renewal of neural stem cells or neural progenitor cells (NPCs). Unlike pluripotent stem cells, which can differentiate into almost any cell type in the body, NPCs are specialized in certain brain regions to become either neurons or non-neuronal cells called glial cells that provide support and protection for neurons.
There are two primary areas of the brain where neurogenesis occurs — also known as neurogenic niches. One region is the dentate gyrus (DG) of the hippocampus, the brain region that plays a crucial role in learning and short- and long-term memory consolidation. The second neurogenic niche is the subventricular zone (SVZ) of the lateral ventricles. In addition to being a source of neural stem cells that can go on to form brain cells, the SVZ is also involved in generating star-shaped glial cells known as astrocytes following a brain injury.
Singling Out Selenium
In this study, Leiter and colleagues aimed to uncover what was going on behind the scenes during exercise-induced neurogenesis. As exercising muscles send out various chemical signals that can influence brain function, they performed a screen of protein levels in the blood plasma of sedentary mice and those who ran on an exercise wheel to look for differences. While they found dozens of proteins altered by exercise, one stood out that was more than doubled in the plasma of active mice — an antioxidant protein that transports selenium into the brain and other tissues, known as selenoprotein P (SEPP1).
After identifying SEPP1 as a potential protein that mediates neurogenesis, the research team took to the lab to study selenium’s role in the process. Leiter and colleagues treated NPCs — the cells that can mature into neurons — with two forms of selenium, sodium selenite (a salt form found in water and soil) or selenomethionine (an organic form found in the diet). Both forms of selenium significantly increased NPC proliferation (growth) and maturation into brain cells — within just 14 days, the number of these neuron precursor cells doubled.
They also looked at the effects of injecting sodium selenite directly into the mice’s brains, finding that one week of selenium infusion tripled the number of NPCs in the hippocampal dentate gyrus, with the majority differentiating into neurons. However, after selenium administration, no beneficial effects were seen in the second neurogenic niche, the SVZ region.
To confirm that SEPP1 was the key protein they were looking for, they studied mice that lacked the gene needed to create SEPP1. When these SEPP1-lacking mice ran on the treadmill, there was no expected boost to NPC growth or maturation, indicating that SEPP1 is required for these neurogenic benefits.
The research team was astounded by these results. As lead researcher Tara Walker, a research fellow in the Queensland Brain Institute at The University of Queensland, puts it, “I’ve been working on neurogenesis for almost 20 years … and we’ve never seen anything like that before.”
Selenium Supports Cognition in the Aging or Injured Brain
Leiter and colleagues then aimed to determine if supplemental selenium could aid cognitive losses in the aging brain. They added selenomethionine to the drinking water of older mice who were about 60 in human years. After one month of supplementation, the results were similarly impressive — the number of new neurons in their hippocampal regions had doubled.
These benefits also correlated with improved cognition, as the older selenium-treated mice performed better than control mice on two mazes and puzzles that test memory and learning abilities. As the authors state in their paper, “Together, these findings indicate that selenium supplementation can restore age-related deficits in hippocampal function.”
Lastly, the research team examined whether selenium supplementation could reverse cognitive deficits after the mice’s hippocampi injuries. The injured mice who received selenium performed comparatively well on memory tests as the normal, uninjured mice. Conversely, brain-injured mice who didn’t receive selenium exhibited significant losses to memory and performance on these tasks.
Skipped the Gym? Try Selenium Instead
While the neuron-building benefits of aerobic exercise have been known for decades, the underlying mechanisms have remained unclear — and now, one piece of the puzzle has been added. With this research, Leiter and colleagues identify that the selenium-containing protein SEPP1 is vital for exercise-induced neurogenesis to take place.
Not only that, but mimicking the effects of exercise with supplemental selenium also restores neurogenesis and reverses aspects of cognitive loss from aging or injuries. As lead researcher Walker concludes, "This is the first study to show that selenium supplementation mediates exercise-induced adult neurogenesis and reverses injury- and aging-induced learning deficits.” While this is no excuse to slack off on your exercise routine, the authors reflect how this research is “particularly important for the treatment of individuals who are unable to exercise due to advanced age, frailty, or disability.”
Selenium deficiency has been linked to a host of brain-related conditions, and blood levels of the mineral tend to decrease with age. As selenium is a readily available and inexpensive supplement — as well as found in many foods, including Brazil nuts, seafood, poultry, and organ meats — it could be easily incorporated into the diet or supplement regimen of older adults to support brain health. One caveat: selenium is toxic when taken or eaten in high doses, so ensure not to exceed the tolerable upper intake level of 400 μg per day in adults. As for the future, study co-leader Hou states that they "will continue to work with our collaborators to study the potential benefits of selenium in other neurological conditions.”
Leiter O, Zhuo Z, Rust R, et al. Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging. Cell Metab. 2022;S1550-4131(22)00005-5. doi:10.1016/j.cmet.2022.01.005