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Miracle-Gro for the Brain

Exercise, BDNF, and Learning 

Not long ago, a mention of brain-derived neurotrophic factor (BDNF) would have elicited a blank stare from all but neuroscientists. Dr. John J. Ratey, a clinical professor of psychiatry at Harvard Medical School, changed that in a big way with the publication of his book SPARK: The Revolutionary New Science of Exercise and the Brain (Little, Brown, 2008). In SPARK, Ratey termed BDNF “Miracle-Gro for the brain.” A massive amount of research, Ratey explained, has shown that BDNF “nourishes neurons [brain cells] like fertilizer.” When researchers sprinkle BDNF onto neurons in the lab, the cells spontaneously sprout new branches, producing the same structural growth required for learning—causing Ratey to think of BDNF as Miracle-Gro for the brain. 

What really sparked Ratey’s interest, however, was a report that, in mice, exercise elevates BDNF throughout the brain. “[That finding] laid the foundation for proving that exercise strengthens the cellular machinery of learning,” Ratey wrote. “BDNF gives the synapses the tools they need to take in information, process it, remember it, and put it in context.” (For more details, see Reboot Your Brain with Exercise in our Aerobic Exercise category.)

More recently, an article by Gretchen Reynolds in The New York Times on exercise and BDNF (November 30, 2011) triggered a flurry of comment. Reynolds related four cutting-edge studies, published in 2011, revealing how exercise stimulates BDNF—and brain function. The new studies involve humans as well as rodents and come from around the world: Ireland, Brazil, and two from the USA.

Brief High-Intensity Aerobic Exercise Improves Memory

In the first study, scientists from the School of Medicine at the University of Dublin gave students a series of memory tests, with and without exercise. They found a chain reaction—exercise, BDNF, learning, and memory. The form of exercise was a first.

Eadaoin W. Griffin and colleagues allocated sedentary male college students (age ~ 22) to three exercise groups and a control group. Before exercise, all of the students watched a rapidly moving lineup of photos with the faces and names of strangers. After a 30-minute break, they were all asked to match the faces and the names. (There was no difference between groups.) The exercise programs began after the initial testing. The memory test was repeated after each form of exercise.

Stationary bicycles were used for all three exercise protocols: a single bout of acute exercise, three weeks of moderate-intensity aerobic training, and five weeks of the same regimen. The control group continued to rest throughout the study. The single bout of exercise called for the students to pedal against slowly increasing resistance until voluntary exhaustion. (Resistance was increased every three minutes.) The three and five week programs were traditional steady state exercise.

Blood samples were taken throughout the experiment to measure circulating amounts of BDNF. The rested volunteers did not register any change in BDNF—or improvement in memory. Notably, two of the exercise groups showed an increase in both.

“The results show that a short period of high-intensity cycling results in enhancements in performance of the face-name matching,” the researcher reported. “These changes in cognitive function were paralleled by increased concentration of BDNF…in the serum of exercising subjects.” Surprisingly, three weeks of cycle training had no effect, but five weeks did. “Increases in fitness, cognitive function and serum BDNF response…were observed following 5 weeks of aerobic training.”

“To our knowledge, this is the first evidence for an acute exercise-induced enhancement in function of these [memory] structures in humans,” the researchers wrote in their report. “It is possible that the effect of chronic exercise on cognition may be mediated by an alternative mechanism involving BDNF,” they added. In short, long and short exercise improve memory, possibly in different ways.

(The Irish study was published in the journal Physiological Behavior.)

The second and third studies that Reynolds reported involved rodents, where more invasive methods can be used to examine underlying mechanisms. Rats can be exercised and tested, and then dissected and analyzed. The second study examined tissue in three parts of the body, while the third focused on BDNF formation in the memory center of the brain.

Five-minute Bouts of Exercise Rejuvenate Brains in Elderly Rats

Brazilian scientists lead by Aderbal S. Aguiar Jr. ran sedentary elderly rats at an easy pace on a treadmill for four to six minutes several days a week for five weeks—and compared the exercised rats to much younger rats on rodent memory tests. They then analyzed changes in the heart, muscle, and brain tissue of the exercised old rats. The findings were nothing short of spectacular.

Not only did this very conservative exercise program increase the oxygen capacity of their muscles and hearts, it reversed age-related learning and memory impairment. “Remarkably, the observed cognitive-enhancing properties of short bouts of exercise were accompanied by [a cascade of biochemical processes in the memory center of their brains] that culminates in the marked increase of… BDNF protein levels [there],” the researchers wrote in summarizing their findings.

Exhibiting typical scientific reserve, Aguiar et al concluded: “We believe that the present indication of the benefits of short bouts of exercise in aging rodents should be considered in further studies addressing the effects of physical exercise in elderly humans.”

(This study was published in the journal Mechanisms of Ageing and Development)

As noted, the third study focused on BDNF formation in the brains of exercising rodents.

Voluntary Running Regulates BDNF 

While it has been shown repeatedly that exercise improves brain function in conjunction with the action of BDNF, the mechanisms involved are not well understood. To learn more, scientists at the Brain Injury Research Center at UCLA studied changes in the brain of rats allowed to run freely for seven days. Importantly, their memory centers abounded with precursor BDNF and mature BDNF not found in sedentary rats. Among other things, they found what appeared to be an orderly progression in the formation of BDNF following exercise.

“These results indicate that the effects of exercise on hippocampus plasticity are dependent on BDNF processing…, with important implications for neuronal function,” the UCLA team concluded. “Exercise appears to act as an excellent homeostatic regulator of BDNF processing and function with important implications for brain plasticity.” Simply put, exercise keeps the level of BDNF within a range that optimizes brain function.

(This study was published in the journal Neuroscience.)

Finally, Reynolds wrote about the role of BDNF in the skill level of aging pilots. Reynolds called it “perhaps the most inspiring of the recent experiments.” It brings the spotlight back around to humans in a real life situation.

BDNF Predicts Skilled Task Performance

Researchers at Stanford University School of Medicine studied 144 experienced pilots ages 40 to 69 who took standardized flight simulation tests three or more times over a two year period. Importantly, they also examined them for a specific structural change in their brain BDNF to determine if it correlated with flight simulation scores. In addition, they measured hippocampal volume in some of the pilots.

They found that the structural change in BDNF did, in fact, predict the rate of decline in cockpit performance scores. They also found that age-related changes in hippocampal volume were significantly altered by the structure of their BDNF.

“We found that val66met substitution in BDNF correlated longitudinally [over time] with the rate of decline in standardized flight simulator score,” the researchers reported. “Furthermore, the rate of decline in hippocampal volume could be significantly affected by this substitution.”

“Our study suggests that val66met polymorphism in BDNF can be linked to the rate of decline in skilled task performance,” the Stanford researchers concluded. 

All of the pilots declined somewhat in cockpit performance over the two-year period. A similar decline with age is common in all of us. In this case, however, the decline was most striking in a particular group carrying a gene variant known to reduce BDNF in the brain.

“Val66met” is short for the “valine-to-methionine substitution at position 66” in precursor BDNF. Men with the variation are called “met carriers,” while those without are “non-met carriers.” The study found that the met carriers showed double the usual decline in cockpit performance, making it quite clear that BDNF formation predicted their cockpit performance. What we don’t know is whether exercise would have slowed the decline by raising the level of mature BDNF.

Dr. Ahmad Salehi, an associate professor psychiatry at Stanford and senior author of the study, told Reynolds that his team plans next to examine the exercise histories of the pilots to see if those with the gene variant responded differently to exercise. Salehi believes that exercise would be especially important to the met carriers. “But for everyone,” he emphasized, “the evidence is very, very strong that physical activity will increase BDNF levels and improve cognitive health.”

“BDNF seems to be key to maintaining not just memory but skilled task performance,” Salehi said.

(The Stanford study was published in the journal Translational Psychiatry.)

*  *  *

Short bouts of exercise stimulate my thought process; no question about it. Some of my best creative thinking is done during the short walks (about 10 minutes) I take morning and afternoon on most days. Exercise helps me connect the dots, so to speak, put related ideas together. Within the first block or so, solutions start coming to me. New words or phrases or better ways to express myself or missing elements pop up, even when I’m spacing out or thinking about something else.

The same thing happens to me during the night, usually after 4 or 5 hours of sleep. I drive Carol crazy turning the light on and off writing notes to myself.

The creative process is miraculous—and accessible. Nothing sparks it like exercise. Sleep is close. Coffee is barely in the ballpark

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