As the forests of Africa gave way to the plains, our ancestors came down out of the trees and started to run. Ancient humans chased down larger prey by working together in sophisticated hunting groups that could follow prey for hours before actually seeing it, using clues to track the animals and infer their movements. In order to run such long distances, hominins grew taller and stronger, developing long legs and tendons, wide shoulders, and weight-bearing joints. This aerobic capacity was unprecedented among primates.

At the same time, ancient humans were quickly evolving more nuanced communication and reasoning skills. With developments in the body and the brain evolving in parallel, pharmacologist Michael Spedding, living in France, and sports scientist Timothy Noakes at the University of Cape Town have postulated that physical activity supported the evolution of complex cognition, and have suggested that exercise may be necessary to keep our brains...

"While early hominins were undergoing intense skeletal and metabolic changes, major changes also occurred in their brains," Spedding and Noakes wrote in a recent commentary in Nature. "We propose that these changes have rendered us dependent on mental and physical exercise to maintain brain health. Exercise doesn’t just help muscles—it activates our brains."

It is widely believed that bigger brains resulted from a shift in the hominin diet to include more meat, which requires less digestion than vegetables, freeing up energy to feed the brain instead. Anthropologist Richard Wrangham famously proposed that cooking our food made meals even easier to digest, increasing the potential for bigger brains. But recently, studies into a protein called brain derived neurotrophic factor (BDNF) have uncovered a more basic link between running after prey and growing bigger brains—exercise stimulates BDNF production. This led Spedding and Noakes to propose BDNF as a central factor in both the mental and physical advances as humans evolved to run.

Carl Cotman first discovered this link between BDNF and exercise in the early 90s when he was studying aging, and realized that more active elderly people experienced slower mental decline. Thinking that increased blood flow to the brain was not sufficient to explain the phenomenon, he began to look for a more fundamental relationship. He discovered a few studies that described BDNF's essential role in neuronal growth and health, and started experimenting with mice. Sure enough, by exercising the animals in wheels, Cotman found that BDNF levels increased in the brain, particularly in the hippocampus.

Further study has revealed just how fundamental BDNF is to maintaining brain health. "It controls things from synaptic plasticity to new synapse growth, promotes neurogenesis in the hippocampus, and plays in part in mediating vascularization," said Cotman. "It's basically like brain fertilizer."

Spedding and Noakes believe that it's this relationship that drove human brains to develop as our ancestors started to run away from the trees and towards meat on the open plains. Indeed, BDNF appears to play crucial roles in building brain areas associated with the task of tracking prey in organized social groups.

"As humans needed more brain power to track prey, increases in BDNF may have helped to build up the hippocampus and prefrontal cortex—key brain areas that are involved in spatial mapping, decision-making and control of context, fear and emotions, including violence," Spedding and Noakes wrote in their commentary.

BDNF comes in several forms, created via alternative splicing patterns of the transcribed gene, and although it is found across the animal kingdom, more varieties are found in humans than any other species. Compared to rodents, regulation of the different BDNF forms is more complex and sophisticated in humans, providing more control over a greater number of BDNF varieties. While the majority of these proteins are found in the brain, they are also in muscle and other tissues, where they can increase protein synthesis and fat metabolism.

Restricting BDNF in mice induces obesity and type II diabetes, ailments readily coupled with lack of exercise, but diminishing BDNF is also associated with stress and psychiatric disorders. Conversely, exercise has been linked to many cognitive benefits, including helping to treat mild depression, Alzheimer's disease, and schizophrenia.

"Putting it all together, we think that exercise increases BDNF in key areas of the brain, which, in turn, has physiological effects that help to protect humans from psychiatric problems," Spedding and Noakes wrote.

But while BDNF levels rise in the bloodstream of people as they exercise, the direct influence on brain function isn't clear. While there is mounting evidence from human studies to support the hypothesis that BDNF was crucial to the developing brain, Noakes said, but this has yet to be shown more definitively. Ongoing work by Cotman and others, such as investigations into the effects of exercise on Alzheimer's, could be the nail in the coffin Spedding and Noakes, both competitive athletes themselves, have been waiting for. But even with details left to be worked out, Spedding and Noakes are pushing the idea of exercise as a way to brain health, as well as bodily health.

Cotman agrees. "I think it's an important principle that there is something you are physically doing to your brain that we know is good for it," he said. "I know sometimes when I'm working out I think, 'Oh boy, my BDNF levels are getting a boost!'"

T. Noakes, M. Spedding, "Olympics: Run for your life," Nature, 487: 295-296, 2012.

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