We were not surprised when our recent research was seriously questioned. After all, we ourselves are still skeptical about what we have seen in the whole survey. However, repeated and diverse experiments have convinced us that our conclusion is correct: in the hippocampus (a very important area for learning and memory) of adults, new brain cells will not grow (or are extremely rare). In other words, the birth of new neurons in human memory circuits dropped to an undetectable level in childhood.
Our findings have sparked a healthy debate, because for about 20 years, brain scientists have always believed that neurons are constantly being born in the adult hippocampus. Whether and how adults produce new neurons is very important for understanding how our brains adapt to the changing living environment and how we can repair brain damage.
With the collection of more and more evidence that helps to improve and revise the theory, science is also making progress. As neuroscientists, according to our recent research, we are also adjusting our ideas about how adult learning must work.
Adult Neurogenesis: Animal Model of Human Since the 1960s, arturo, one of us, has been studying how new neurons are born and integrated into brain circuits. He is a member of Fernando Nottbohm's Rockefeller Laboratory, which published a series of groundbreaking papers at that time, indicating that songbirds produce new neurons in their brains every season when they are ready to learn new songs. In the early 1960s, it was found that the brains of rodents would produce new neurons in adulthood, but this view has been controversial. Until Nottbohm's songbird research convinced most neuroscientists that the adult brain can produce new neurons, several studies found signs of new neurons in the hippocampus of adults, which made many researchers accept that this part of the brain can also update itself in human life. This idea has aroused people's interest in studying how to increase this regenerative ability, which may avoid the decline of brain function related to age.
In fact, we ourselves began to look for new neurons in the adult hippocampus, because previous human studies estimated that 700 new cells were born in the adult hippocampus every day. We hope to compare this phenomenon with another area of the brain. We recently reported that there are far fewer new neurons in this area than those found in other animals.
The evidence collected proved to be negative. When arturo visited the laboratory of Yang Zhengang, a collaborator of Fudan University, some different phenomena appeared. China studied several well-preserved human brain specimens. When arturo returned to the laboratory from China to share the observation results of new neurons missing in adult hippocampus with Mercedes and Sean, we faced a challenge: how to prove it negative? How can we be sure that we haven't missed the new neurons seen in other studies? As some critics have pointed out, it is very complicated to identify new neurons in human brain tissue. Usually, researchers look for protein, and we know that these protein are produced by young neurons. But we are studying the brain samples donated by the deceased. Maybe these "recognition" protein will degrade after death. They may also have other functions and are produced by other types of cells.
So we need to use a variety of methods to find new neurons. First, we found some different protein in young neurons. Next, we studied these cells carefully with high-resolution optical microscope and electron microscope. We want to make sure that any cells we report have the unique appearance of young neurons; They usually have a simple shape different from mature neurons, which are usually large and have long and thin branches. We also observed the general pattern of gene expression in this region, and observed a similar decline in genes related to young neurons. In addition, we also look for evidence of stem cells that make young neurons. They have their own protein markers, which can be detected during division.
None of the adult hippocampal tissues we tested with these techniques showed evidence that young neurons or their parents split stem cells.
To ensure that our technology can even detect young neurons or split nerve trunks. When we knew that hippocampus should exist, we observed the same area of hippocampus before birth. In these fetal brain samples, we can clearly see a large number of new neurons. Using the same technique, we look for these cells in the brain tissues of people who died in infancy, childhood or early adolescence. We saw a sharp decline in the number of new neurons until 13 years old. By the age of 18 and 19, we couldn't find any neurons. If neurogenesis in adult hippocampus continues, this is a very rare phenomenon.
Can't we see that these cells may be caused by unknown differences between young and old brain tissues? We know that there are very rare young neurons in other parts of the adult brain, so we observed these areas. When we can easily find these rare young neurons, we will become more confident. What we see or can't see in the hippocampus is not only the product of aging brain tissue.
It may be related to the patient's medical history before his death, or the way the samples were collected covered up the evidence that new neurons appeared when the brain was still alive? In order to convince us that these organizations represent the adult brain as much as possible, we studied the brains collected by many different collaborators around the world and saw the same results.
Will the time from death to brain preservation prevent us from detecting young neurons? To verify this, we collected tissue samples from more than a dozen patients whose brains were removed during surgical treatment of severe epilepsy. These samples are quickly collected and preserved by us to maximize their quality. In addition, we observed two samples, and the brain was collected and preserved almost immediately when it died. We saw the same result.
We examined 59 brains, which is equivalent to previous studies. In all these cases, we all see the same result: there are no signs of new neurons in the adult hippocampus. Our conclusion is that it is extremely rare if new neurons are born in the hippocampus of adults.
So, what did other researchers find that made them believe that new neurons were born in the hippocampus of adults? Previous studies usually used only one protein to identify new neurons. Unfortunately, we found that the most common protein, a kind of protein called diclofenac, can also be found in non-nerve brain cells (called glial cells), which will regenerate all their lives.
Another research team tried a different technique more commonly used by archaeologists and geologists: carbon 14 dating. This is a very creative method to determine the age of cells, especially in the field where we need new methods to study the human brain. However, it is not clear to what extent this method can accurately identify neurons, or whether there are other reasons that lead to the change of radioactive carbon level beyond cell division, thus producing new neurons.
A lot of research has been left, and our research has also left us with a lingering question-why is the incidence of neurogenesis declining? Why does the hippocampus continue to produce new neurons in other animals, not in humans, until adulthood? In order to solve this problem, we have studied the hippocampus of macaques, and the hippocampus will constantly produce new neurons in adulthood. Using the labeling technology that humans usually can't use for ethical reasons, we tracked the generation of new neurons in living animals. We found that neural stem cells that produce new neurons gather in the strips of monkey hippocampus before birth. This layer even exists in young monkeys and contains splinter cell. When we review the data of newborn human hippocampus, we find that stem cells do not organize themselves in this way-this is the obvious difference between the development of human brain and that of other primates.
Our research only involves the hippocampus; Many other brain regions in the human brain-they are very large-have not been studied, and whether there may be new neurons remains to be explored. Developing a better method to directly study the human brain will help researchers to know more about how the plasticity of human hippocampus occurs. Future research can determine whether there is a way to re-trigger the birth of new neurons in this area.
But what does our discovery mean? Should we bemoan the lack of new neurons in adult hippocampus? We don't think so.
First of all, the process of making a new neuron is fascinating and teaches us a lot of new things. Adult nerve exists in birds, mice, rats and other species and should continue to be a research field. One day, this work may teach us how to induce this phenomenon in the brain.
Second, although rodents have a large number of new neurons, our brains have been running for decades-much longer than mice's brains. In fact, human longevity may be related to the decline of hippocampal nerve; We may not have progenitor cells in childhood.
Our research also raises new questions-obviously, a rich and healthy lifestyle can really improve our brain function and delay aging, even without new neurons. Deepening the understanding of human brain development may provide new treatments for brain diseases in the elderly.
Shawn Sorrells, postdoctoral fellow in neurosurgery at the University of California, San Francisco, arturo alvarez Bila, professor of neurosurgery at the University of California, San Francisco, and Mercedes paredes, assistant professor of neurology at the University of California, San Francisco.
This article was originally published in Dialogue. Read the original. Pay attention to the voice problems and debates of all experts on Facebook, Twitter and Google+ and become part of the discussion. The views expressed are those of the author and do not necessarily reflect those of the publisher. This version of this article was first published in Life Science.