Story at a glance…

• Selenium was found to pair with exercise’s beneficial effect for hippocampal health.

• Exercise in mice greatly increased blood content of the blood-brain selenium transporter.

• Dietary selenium was found to increase brain stem cells, increase neurogenesis, and reverse cognitive decline in old mice.

Selenium was found in a study to act as the mechanism for exercise’s effect on brain regeneration, and that this inexpensive mineral reverses cognitive decline in aging and in hippocampal injury.

Looking at the blood of regularly-exercised mice, scientists recently found that their bodies were producing a protein designed to shuttle selenium into the brain, in much higher quantities than in mice that weren’t able to exercise.

In total 68 proteins were upregulated in the running mice, and selenoprotein-P (SEPP1) was one of the most upregulated, appearing in twice the amount found in the blood of non-runners. 25 proteins move selenium around our bodies, but SEPP1 is the most important for maintaining selenium levels in the brain. It moves 10 molecules of the selenium-carrying amino acid selenocysteine, at a time, where most other selenoproteins move merely 1.

The purpose of this work was to establish that since it’s known that selenium induces adult hippocampal neurogenesis, meaning the creation of new neurons in the brain’s hippocampus region, could selenium supplementation create an exercise-like reaction in the shuttling of selenium to the brain, increase hippocampal neurogenesis, and delay age-related cognitive decline?

As animal life evolved, it had to be able to learn, map territory, and establish basic memories of things like signs of danger or signs of food. This is the domain of the hippocampus and many species of mammals, birds, reptiles amphibians, and even fish, have been found to have hippocampi; and that they all work in much the same way.

With the hippocampus so critical in turning experiences into information, the genesis of new hippocampal neurons had to continue across the entirety of the animal’s life.

It’s been known that exercise controls the genesis of new hippocampal neurons since at least 2003, but the way in which it does this, the biological mechanism, remained hidden.

Selenium rescues old brains

Within exogenous hippocampal cells, those grown with inadequate selenium produced significantly fewer neural precursor cells than did those supplemented with high amounts of selenium. These “NPCs” are like stem cells, and can rapidly become hippocampal cells under the influence of exercise.

Having confirmed that in vitro cells responded positively to selenium, the researchers experimented in vivo, and found that in two different delivery doses and two different locations, the increase in neural precursor cells in a particular region of the hippocampus called the dentate gyrus was consistent.

The tiny quantity of 55 nano-molars in direct selenium infusion increased net-neurogenesis by 55% 3 weeks after a 7-day infusion program. The total neural precursor count was 300% higher than normal levels in mice at the end of the 7 days, which the scientists took to mean that selenium-induced increases in neural precursors bettered the overall longer-term survival rate of those cells.

In a series of pilot experiments, the researchers wanted to see if selenium’s effect on brain cells could be replicated in mouse models where the mouse in question was very old, and with dietary supplementation since the infusions were found to cause tissue damage.

“It has previously been shown that the age-related decrease in plasma selenium levels in humans positively correlates with the probability of cognitive decline,” the authors write. “We then investigated whether dietary selenium supplementation was sufficient to rescue the age-related decline in proliferating precursor cells, [and] our results revealed that 18-month-old selenium-treated mice had significantly more proliferating NPCs… than control mice”.

To test whether this increase in neural precursor cells resulted in an increase in hippocampal function, the researchers used a common trial in which mice are put on a rotating platform on which a small section would deliver a very mild shock if stepped on. Visual cues can help mice figure out where the shock section is in order to avoid it, and the faster they piece the puzzle together, the better it’s written their capacity for spatial memory is.

“[W]e show that mimicking the exercise-induced increase in systemic selenium transport by dietary selenium supplementation can restore neurogenesis and reverse the cognitive decline associated with aging and hippocampal injury,” the authors write.