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Wired to Run—and Think 2012

"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!'"

Treadmill Exercise Induced Functional Recovery after Peripheral Nerve Repair Is Associated with Increased Levels of Neurotrophic Factors

We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration.

Exercise switches off genes for depression?

intriguing 2015 study, physician Helmuth Haslacher and his colleagues at the Medical University of Vienna in Austria compared the mental health and genomes of 55 elderly marathon runners and endurance bicyclists with those of 58 nonathletes. Among the nonathletes, they found a statistically significant correlation between the number of depressive symptoms these individuals experienced and a particular gene variant that interferes with normal BDNF production. Among the athletes, however, there was no such correlation. The researchers concluded that by stimulating BDNF production, long-term, vigorous aerobic exercise might actually counteract a genetic susceptibility to depression.

Differential effects of acute and regular physical exercise on cognition and affect. - PubMed - NCBI

Participants were evaluated on novel object recognition (NOR) memory and a battery of mental health surveys before and after engaging in either (a) a 4-week exercise program, with exercise on the final test day, (b) a 4-week exercise program, without exercise on the final test day, (c) a single bout of exercise on the final test day, or (d) remaining sedentary between test days. Exercise enhanced object recognition memory and produced a beneficial decrease in perceived stress, but only in participants who exercised for 4 weeks including the final day of testing. In contrast, a single bout of exercise did not affect recognition memory and resulted in increased perceived stress levels.