Authors: Jörg Blech
Yet some findings remain mysterious. Why is it, for example, that the capability to grow new nerve cells is restricted only to a part of the forebrain and the dentate gyrus of the hippocampus, an area important for learning and memory? This limitation seems even stranger because most other parts of the brain have progenitor cells and stem cells, which have the biological potential of maturing into fully functional neurons. But instead of doing this, they lie dormant, the sleeping beauties of the brain.
To awaken these cells and make them grow is a dream of medicine already pursued by many pharmaceutical companies as well as academic researchers. Brain, the motto goes, heal thyself!
THE MYTH OF THE STATIC BRAIN
This hope and excitement centers on a phenomenon that was doubted and dismissed by almost all neuroscientists in the last century. They were under the influence of a verdict by the famous Spanish brain researcher and Nobel laureate, Santiago Ramón y Cajal. In 1928, he famously declared: “In adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may regenerate.”
A few scientists dared to question this verdict but were not taken seriously and were even ridiculed. One of these skeptics was Joseph Altman, who carried out fascinating experiments at the Massachusetts Institute of Technology (MIT) in the 1960s. He fed food that contained low-level radioactive chemicals needed to make DNA to rats, cats, and guinea pigs. If the animals produced new nerve cells, they would incorporate the radioactive labeled chemicals into the nuclei of these new cells. And indeed, Altman was able to detect radioactive signals in the brain tissue after he killed the animals and performed autopsies on them—a sure sign that neurogenesis had occurred. In hindsight, it seems odd, but other researchers simply ignored Altman’s findings. This neglect harmed Altman’s career; he was forced to leave MIT and take a position at a less well-known school.
Ten years later, the researcher Michael Kaplan of the University of New Mexico took pictures with an electron microscope showing newly grown neurons. But he was ignored and ridiculed as well. Kaplan once recounted how the influential neuroscientist Pasko Rakic of Yale University dismissed his results: “Those may look like neurons in New Mexico. But they don’t in New Haven.”
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Rakic even came up with a theory why neurons in the adult brain were unable to divide: at one point during evolution, our forebears had traded the capability of producing new nerve cells for the ability to store memories in a constant number of nerve cells. For reasons of stability, Rakic believed, there was simply no space reserved for new neurons in the human brain.
Eventually, singing canaries greatly contributed to overturning the old, false dogma of the static brain. The male birds sing their songs in the spring, but over the summer lose their repertoire like feathers in the molt—only to impress female birds the next spring with a completely new set of melodies.
One day, as he was taking a shower, it occurred to the biologist Fernando Nottebohm of Rockefeller University in New York how the male canaries accomplish this trick: the areas of the brain containing the memories of the old melodies die off and are replaced by new neurons the next spring. Experiments using radioactive DNA have confirmed Nottebohm’s hunch: male canaries indeed produce thousands of new nerve cells per day.
Initially, it was believed that only birds were capable of regrowing brain tissue. But when scientists looked into other species, they found neurogenesis all over the place: frogs, lizards, rodents, and monkeys do it. Why, then, should humans be an exception?
It took quite a while to come up with the ultimate proof. But in 1998, Swedish and American brain researchers realized there was a way to see if neurogenesis takes place in the adult human brain. Physicians routinely inject radioactive, labeled DNA building blocks into severely ill cancer patients. By doing so, they are trying to find out how many new cancer cells grow in a patient’s tumors. However, because the labeled DNA is incorporated into any type of dividing cells, new nerve cells should be detectable, too. The researchers were granted permission to study five patients with advanced cancer of the larynx. After their deaths, the patients’ brain tissue was analyzed. The result? Until the last days of their lives, these people had produced new neurons in their brains.
Since this milestone discovery, researchers agree that an adult produces thousands of neurons in the hippocampus every day. In comparison to the roughly 100 billion neurons that comprise the brain, this might appear a small amount. However, the new neurons possess a juvenile excitability lost by the old neurons. The neuroscientist Gerd Kempermann is convinced they have an important impact on our mental capabilities: “Apparently a rather small number of newly produced cells is sufficient to profoundly alter the network architecture of our brain.”
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It is evident that freshly produced neurons greatly contribute to a phenomenon called neuroplasticity, the brain’s surprising capability to adapt to a constantly changing environment. At least three different mechanisms contribute to the plasticity of the brain. First, existing connections between nerve cells, the synapses, can be strengthened within seconds, allowing us to remember what we just heard, felt, or thought. Second, as new synapses sprout, they create a dynamic neuronal network that can store memories for long periods of time. Finally, the production of new nerve cells—a process that takes many days—can bring enduring changes upon the brain. Many studies have added weight to the belief that neurogenesis is an “important part of plasticity,” says Amelia Eisch of the University of Texas Southwestern Medical Center in Dallas.
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In short: a few extremely versatile neurons are pivotal for the brain’s lifelong ability to change itself. Like a muscle that grows when used, the cells of the gray matter thrive when challenged. New neurons in the olfactory bulb develop when they encounter odors, and new neurons in the hippocampus mature when they receive input worth remembering.
BRAIN FITNESS
The phenomenon of neurogenesis could actually be the long-sought mechanism by which the environment is able to shape and put its imprint upon the brain. Many empirical studies have shown how important physical activity is among these environmental influences. Both physical and cognitive exercises appear to prevent or delay degenerative processes in the aging brain. Researchers at Rush Presbyterian-St. Luke’s Medical Center in Chicago carried out a study of 642 elderly people with varying educational backgrounds. It turned out that with each additional year of formal education, the risk of developing Alzheimer’s disease was reduced by 17 percent; several other studies also suggest that a good education can stave off the onset of Alzheimer’s.
In the late 1980s Robert Katzman of the University of California in San Diego studied this effect in more detail. In his view, learning and studying increases the density of the synapses in the brain—thereby enhancing something called “cognitive reserve.” The bigger the cognitive reserve, reasoned Katzman, the better the brain can cope with the loss of nerve cells due to illness and age.
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This concept was supported by a study of 130 Catholic priests and nuns. During their lives, their cognitive capabilities were assessed. After their natural deaths, autopsies on their brains were performed. Plaques (protein deposits that interfere with neural networks) typical of Alzheimer’s disease were found in all brains with the same frequency, regardless of the level of education each had received. It turned out, however, that these plaques affected the brains in varying degrees. Those people with an extensive education had retained their cognitive capabilities much better than people with less education. The differences were profound: better-educated individuals started to show symptoms of Alzheimer’s only when they had five times as many plaques in their brains as people with lower levels of education. The former group possessed a substantial cognitive reserve enabling them to compensate for the effects of Alzheimer’s.
Your current occupation—reading—as well as playing cards, or doing crafts, can help preserve the cognitive functions, believes the neurologist Robert Friedland at the Case Western Reserve University in Cleveland: “I believe they all involve learning in some way.”
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That would mean an interesting job keeps one healthy, whereas retiring early in life might be a fatal step toward dulling the mind.
In any case, watching television should be avoided. According to Friedland’s research, gawking at the screen increases the risk of being afflicted with Alzheimer’s disease. He and his colleagues asked the partners and relatives of 135 Alzheimer patients about their activities before the onset of the disease.
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Subsequently, they compared these data with answers from 331 healthy people. The study results reveal that the Alzheimer’s patients spent a much larger part of their lives in front of the television set than healthy people. With each hour of watching television per day, the risk of Alzheimer’s increased by a factor of 1.3. That does not necessarily mean the content of television programs dulls the mind (though there is no shortage of stupid shows), but rather frequent television consumption might point toward a lifestyle lacking both physical and mental activity. “Time spent on television viewing may reflect a desire to avoid more stimulating activities and may be indicative of a mentally inactive lifestyle which has been shown to be associated with increased risk of cognitive decline with age,” the authors conclude.
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Conversely, an active lifestyle turns out to be an effective remedy against this cognitive decline experienced by so many elderly people. Ulman Lindenberger and Martin Lövdén at the Max Planck Institute for Human Development in Berlin have followed 516 persons at ages 70 to 100 and recorded the degree of their “social participation.”
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In interviews they asked specific questions about their daily lives: Did they have company the day prior to the interview? Have they recently been involved in hobbies? How often did they dine out, and did they still go to social events like concerts? The data covered a period of eight years and revealed that activity, possibly by triggering beneficial neurological processes, can protect the brain. People who led an active and engaged life showed a significantly smaller cognitive decline than people with limited social participation. An active lifestyle after retirement can mean many different things: music, sports, strenuous playing with grandchildren, studying a language, political activism, hiking, or writing a book. These and other similar activities can serve to keep the brain young.
Physical exercise further enhances this effect. Lindenberger explains this using the example of crossing a street on foot: usually, this task would be more demanding for the brain of an 80-year-old person than for the brain of a teenager. However, if an old person keeps his body in good shape by regular exercising, the attention needed for the motor task of crossing the street is minimal. “Thus, mental energy is saved and can be utilized for other purely cognitive activities,” Lindenberger explains. His example shows how the model of “cognitive reserve” must be expanded. Not only mental activities, but also physical activities, contribute to the resilience of the brain.
Cancer: A Growing Case for Exercise
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BOUT 50 EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT PHYSICAL exercise reduces the risk for colon cancer. In a scientific first, researchers at the Fred Hutchinson Cancer Research Center in Seattle were able to demonstrate this protection on the level of individual cells. Their study included 102 healthy men, who were divided into two groups. Half the participants were asked to conduct one hour of aerobic activity per day (six days a week); the other half carried on with life as usual. After one year, the doctors took colon tissue samples, biopsies, and examined them under the microscope. That way, they were able to detect how many of the colon cells were about to divide. A jump in cell division can be a warning sign of cancer.
The analysis revealed that there were fewer actively dividing cells in men who exercised diligently for an average of four hours of activity per week. Those with more than five hours of weekly exercise demonstrated an even smaller rate of proliferation. The other half of the men, who hardly exercised at all, did not have the beneficial effect.
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Besides colon cancer, breast cancer can be prevented by physical activity. Even when women become active after entering menopause, they lower their breast cancer risk by 20 percent. To see this effect, it is sufficient to be active for 30 minutes for five days per week, doing things like brisk walking or bicycling. The advantages were biggest for slim and slightly overweight women. Though obese women did not profit, they, too, can reap the benefit by reducing their weight to normal and making themselves more likely to realize the preventive effect.
One large study in Europe has even revealed that chores and housework, such as vacuuming, cooking, washing, ironing, and housecleaning, can help stave off cancer. The researchers assessed the activity levels and the health status of 218,169 women for more than six years. Active women spent an average of 16 to 17 hours a week on household chores—and had a reduced breast cancer risk of 20 percent (younger women) to 30 percent (menopausal women) compared to inactive controls. The researchers are not saying that women should be stay-at-home mothers doing all the chores. Rather, the study reiterates a message that is true for both genders: the benefits of exercise kick in at relatively low intensities.
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