“The truth” that was not true at all
We all know that it doesn’t hurt to question established “truths” from time to time. In the mid-1990s, some scientists in California decided to take a good look at the question of whether the adult brain can produce new cells. They didn’t start off by examining human brains, focusing on those of mice instead. The first question they wanted to clear up was if anything would happen in the brain if the animals were removed from their boring, sterile cages and got more stimulation in what scientists call an enriched environment. The mice lived for one month in a cage with plenty of tunnels to hide in, wheels to run on, and toys to play with. They also had the company of more mice. This was indisputably a far more fun environment than the sterile cages the mice were used to. The scientists knew that a change of environment with new experiences could create new connections among the mice’s brain cells, because connections are created when we learn something new. But could it affect the animals’ brains in some other way? It did indeed!
The new, stimulating environment had a huge effect in the brain—it created lots of new cells. Part of the hippocampus had grown, and the results were dramatic. The number of cells had increased by 15 percent in a few short weeks, which was sensational.
This couldn’t be explained by the mice’s young age, because the same thing occurred when they performed an identical experiment on older mice. The animals’ brains didn’t just generate new cells; they seemed to work better. When the mice’s memory was tested by lowering them into a pool in which they had to find a hidden platform, the mice who had stayed in the enriched environment located the platform faster. They also had better memory than the mice that spent their days in a sterile cage.
What exactly caused this effect?
This discovery brought up stunning implications. Could this also apply to people who were put in a more stimulating environment? Did this mean that a change of environment and new experiences such as travel, a career change, or a new social circle could lead the brain to create new cells? Could such experiences improve our memory, and perhaps even make us smarter?
First, let’s back up a step. What was it in the mice’s environment that made their brain create more cells? Was it the toys and the tunnels where they could hide, or was it that there were many other mice around? Or could it have had something to do with the wheel they were running on?
Had it been my guess, I would have ventured that it was a combination of all the factors. Turns out, I was wrong. When the mice only ran on the wheel and didn’t have access to any other stimulus in their crate, the impact in their brain was widespread. It appears that physical activity—running on the wheel—was the principal factor in the creation of new brain cells. Other stimuli, from toys and tunnels or friends, appeared to have little or no effect.
Finding out that regular running produces so many new brain cells had significant repercussions for several of the scientists. One of them, geneticist Fred “Rusty” Gage, told of how his colleagues had turned their lifestyles around completely and begun running as soon as they saw all the new cells in the mice’s brains. They reasoned that if it works in mice, it probably works in humans, too.
But were Gage and his colleagues correct in inferring that the adult human brain could generate new brain cells? This is a difficult question to answer, because it would require studying the brain under a microscope, since a CT scan or MRI cannot provide any clues. In fact, what is needed is an autopsy of a human brain. Even if someone agreed to donate their brain in the name of research after their death, there would still be a problem: How do you figure out if the brain cells are new? It’s extremely challenging to tell the difference between old and new brain cells.
Even adults generate new brain cells
The solution came when Peter Eriksson, a Swedish neuroscientist, had a brilliant idea. Oncologists use a substance called bromodeoxyuridine (BrdU) to decide whether cancer cells divide and whether the cancer grows. In fact, BrdU can tag new cells—not just cancer cells, but other types of cells, as well. Eriksson realized that if new brain cells were present, BrdU would be able to tag them, too, making it possible to pick them out in the brain samples of deceased cancer patients.
DO YOU FORGET PAIN?
I’ve heard the lament “Never again” many times from marathon runners who have just crossed the finish line. And yet, a few weeks later, there they are, signing up for another race. How is it that you can go through a race that you consider intolerably difficult and still choose to line up at starting blocks year after year? A possible explanation is that runners forget how exhausting the event was.
Selective forgetfulness is not some pseudopsychological term, but a medical reality that happens at times such as after childbirth. When a comparison was made between the pain women experienced during labor, at the moment, and the pain they felt after gynecological surgery, it showed that those who had given birth and those who had had surgery rated the pain at about the same intensity. In these cases, the pain of childbirth appears to be comparable to that of a surgical operation.
But when you ask those women to think back and remember the event and the pain a few months later, it turns out that the women who gave birth no longer remember how traumatic it was (at least, not to the same degree). However, those who had undergone surgery remembered the pain as vividly as the day it was performed. Indeed, some women forget how painful it is to give birth. It’s one thing to remember that it is painful, but another to remember the intensity of that pain. From a biological perspective, this isn’t so strange, because if there’s one thing that’s vital for our species, it’s procreation—making more people. That’s why it makes sense that we have a natural mechanism that helps us forget labor pain, or in any case for not remembering the pain in so much detail as to not want to give birth again.
The same thing appears to happen with hard physical exertion. When marathon runners who just crossed the finish line graded the pain they felt throughout the race, the average answer was 5.5 on a scale of 10. When they thought back to that race and graded their pain again three to six months later, their answer went down to a 3. They seemed to have forgotten just how painful it was!
Certainly, selective memory is reasonable from a biological perspective. If we remember how hard it was to follow our kill over long distances, it may discourage us from hunting. However, if we forget how tiring it was, we’ll be eager to hunt again, increasing our chances of getting food and, in the long run, of survival. This is a likely explanation for our memory’s ability to selectively forget the pain inherent in physical activities.
The researchers obtained permission to examine the brains of five deceased patients to look for new cells. Their brains offered a unique insight into the question of whether the brain regenerates throughout life, one of neuroscience’s biggest conundrums. It was hoped that, upon examination, the samples would reveal new brain cells marked with BrdU in at least one of the five donors. They found cells in all five of them, and in exactly the same area of the brain as the new cells they found in the mice—the hippocampus.
Incredibly, it was possible to ascertain that the new brain cells were only about a month old, meaning that they had formed while the donor was dying from a serious illness. The brain had still kept on creating new brain cells! It was also visible through the microscope that the new cells had made connections with older brain cells and appeared to have integrated in the hippocampus, meaning they had assimilated into their new environment. It’s likely that they functioned and were useful while the patient was still alive.
The significance of the donors’ brains containing newly created brain cells was enormous. The news that neurogenesis—the creation and development of new nervous tissue—happens even in adults was a sensation, and it made the headlines in newspapers all over the world. Textbooks in the medical field had to be rewritten. The “truth” that brain cells can’t regenerate over a lifetime was proven to be false.
However, as is so
often the case in the world of scientific research, one answered question usually begets additional unresolved issues. Now the big question was: Does regeneration of cells happen at the same rate no matter how you live your life, and if not, what is it influenced by? Is it possible to speed up this regeneration, and if so, how? One reasonable area of focus would be the influence of physical activity, since studies have already shown how activity produces the best results with mice.
So, is this it? Do we know for sure that exercise leads to a higher rate of brain cell regeneration, even in humans? And do we improve our memory by being physically active? The answer to both those questions is yes. At least, that is the conclusion reached after two decades of research conducted since the discovery of human neurogenesis.
Earlier atom testing could solve the question
Before we continue, let’s ask the following question: How important is the regeneration of new brain cells in the hippocampus? Is it only important to scientists? Is it something that is only visible in laboratory experiments but lacks practical significance? To start, regeneration of brain cells is far from insignificant. Approximately one-third of all the cells in the hippocampus are swapped out for new cells over our lifetime.
One can wonder, how are we to know this? When the brain of a deceased person is examined, you can’t tell if the cells were made when the person was an adult or if they were present throughout his or her lifetime. The methods used by Fred Gage and Peter Eriksson only showed if the cells had been created recently—after the BrdU was introduced.
To solve this mystery, scientists at Sweden’s Karolinska Institute used something that we might not immediately associate with neuroscience: test detonations of atomic weapons.
A lot of blasts were performed during the Cold War of the 1950s and 1960s, many of them in the far-flung islands in the Pacific Ocean. Even though the tests took place on the other side of the globe, the radioactive isotope C-14 got into the atmosphere and spread throughout the world. The concentration of C-14 in the atmosphere has been measured regularly, making it possible to see how much of it has been in the air over the years.
What does this have to do with brain cells? Well, every time a new brain cell is generated, new DNA is created, and C-14 of the same concentration as was present in the atmosphere the year the cell was generated is built right into the DNA’s helix. This means you can date a cell if you know the atmosphere’s concentration of C-14 over the years. A brain cell that is forty-five years old in a forty-five-year-old man will have been there since the man’s birth, while a brain cell that is thirty years old would have been created when the man was a teenager.
Using this method, we can date hippocampus cells in deceased donors who were about ninety years old when they passed away. We can calculate how many cells were the same age as the donor, and how many were younger. The result showed that almost a third of the cells had such concentrations of C-14 in their DNA, indicating that they must have been created after birth. In fact, the tests show that 1,400 new cells are generated in the hippocampus of an adult brain every day. This means that every second of every hour of every day of your adult life, a new cell is created in your hippocampus.
New cells are important for our well-being
Research hasn’t only been able to show that large numbers of new cells are created in the hippocampus over your entire life. We now know that regeneration of cells not only strengthens memory, but is also pivotal to our mental well-being. Many believe that depression is an illness caused by poor nerve cell regeneration, and that the lack of new cells is the true cause of depression, as we touched on in the chapter The real happy pill.
A clue to this hypothesis is that antidepressant medication boosts the regeneration of brain cells. If you block the brain’s ability to create new cells in animals, it will render the antidepressants useless and the depression will not clear. In other words, a person may become unresponsive to antidepressants if the brain can’t create new cells. This strongly suggests that regeneration of brain cells is critical to our sense of well-being and our ability to recover from a depression. If our ability to generate new brain cells decreases, we may start feeling low, become depressed, and exhibit poorer memory; in contrast, we know that being active can double the regeneration rate of brain cells—it truly has that much of an impact.
Move more and develop a more nuanced worldview
The hippocampus, our memory center, is made up of several parts. Neurogenesis happens primarily in one of these parts—the gyrus dentatus—the dentate gyrus. It’s interesting that the production of brain cells happens right in that spot. The dentate gyrus has a very specific function that is important for what is called pattern separation, the ability to register small, subtle differences in what is happening around you, compared to earlier events. Let’s say you enter a room where a cocktail party is in full swing. One of the guests is your sister, a few are close friends of yours, and a few others are casual acquaintances that you have only met a few times. There are also some people you’ve never met before.
When you see your sister, you recognize her immediately. Your brain doesn’t have to work very hard to identify her. Same goes with your friends. However, when you see people whom you’ve only met once or twice, your brain begins matching their faces to what is in your memory bank. “Who is that? I know her so well. She looks like someone from my old job, but no—that’s not her, because she was taller and had lighter hair.”
When you must think so hard that it hurts to try and remember who is in front of you, your dentate gyrus is in overdrive trying to match the face with memories of people you’ve met before. By sifting through minute differences in, say, hair color, height, or facial features, the dentate gyrus is trying to decide if you know this person. He or she can remind you of someone else, and it is by noticing the little details that you’ll figure out if this is someone you have met before or if he or she is completely unknown to you.
Much of what we experience resembles things we have already lived. Think back at what you’ve done today. How many activities were truly unique, things you’ve never done before? Probably not much is distinct, unless you live a very varied life.
Even though many things remind us of stuff we’ve done before and many people we meet remind us of others we’ve crossed paths with, it’s up to our brain to store information on similar events and people as separate memories that can be told apart. That’s what pattern separation is: the crucial ability to have a nuanced view of our environment. Without it, our memories would just flit together into a fog and render us incapable of telling one from the other. Consequently, the regeneration of cells happens right in the part of the brain that is important for pattern separation. You can assertively claim—especially if you are physically active—that exercising improves the odds of having a more nuanced worldview. Personally, I believe that this could be why physical activity is so effective in treating depression.
A person suffering from depression leads a reduced emotional life and ends up missing life’s little subtleties—he or she feels that things are gray and dreary. On the other hand, the opportunities of catching a more nuanced glance at life—and glimmers of hope—may just increase thanks to the regeneration of brain cells in the dentate gyrus.
Does only exercise count?
Does only exercise count in increasing the regeneration of brain cells? Can more stimulating surroundings—what scientists call an enriched environment—also be important for the brain’s ability to create new cells? Yes, environment also plays a role. How many new cells we make doesn’t only depend on how many cells are created, but also on how many of those cells we get to keep. New brain cells are incredibly fragile, and only one in two cells survives. However, it looks like it’s possible to raise the odds of survival so that more of them can make it. In animals living in a more enriched environment, about 80 percent of new brain cells remain viable.
Exercise and physical activity favors the production of additional brai
n cells, and a stimulating environment increases the odds that those cells will survive. It’s totally logical that these two are linked: we have evolved to experience new environments and events as we move about, and the brain is prepared to take in new information. To increase our ability to remember what we experience, new cells are created in the hippocampus. Then, what we experience as we move around in this new environment provides the stimulation that ensures the survival of these cells.
We can conclude that exercise and physical training lay the groundwork for the brain to learn new things. Is it now beginning to seem less strange that we can recall up to 20 percent more words if we walk while we listen to them? I thought so.
Our inbuilt emotional brake and GPS
While the hippocampus helps us build long-term memories, its responsibilities don’t end there. The hippocampus is also important for its ability to help us put things into perspective and compare what we’re experiencing presently with other memories so we don’t overreact emotionally. Furthermore, it plays an important role in our ability to place ourselves spatially, like a brain GPS that keeps track of our position and allows us to store memories of places (a discovery that was awarded the Nobel Prize in Medicine in 2014, by the way). As we read this, specific cells in the hippocampus signal where we are inside, or outside, the room. If we move by a few inches, other hippocampus cells that function as “place cells” become active and create an inner map of our surroundings.
The Real Happy Pill Page 13