New research suggests that the human brain does not add more neurons to its circuitry once it has reached maturity.
The work, published Wednesday in Nature, contradicts a smattering of earlier studies that found that humans did indeed have the ability to add to their neural networks even after they reached adulthood.
Amar Sahay, a professor at the Harvard Stem Cell Institute who was not involved in the research, said the new findings are sure to make a splash.
"But that's science," he said. "It's not always a straight line from point A to point B. Sometimes it's a winding road."
Researchers have known for decades that many animals—including mice, canaries and monkeys—have the ability to produce new neurons over the course of their lives in the process known as neurogenesis.
A small number of papers had indicated that adult humans also possessed this capability, specifically in an interior region of the brain known as the hippocampus that is associated with memory.
However, after examining brain tissue samples collected from 59 human subjects ranging in age from a 14-week-old fetus to a 77-year-old man, the authors found that neurogenesis drops off considerably in humans after one year of life. After adolescence, it appears to stop completely.
The findings came as a bit of a shock to the research team from the University of California, San Francisco
"We went into this work thinking we were going to find evidence of neurogenesis because other groups did," said Mercedes Paredes, an assistant professor of neurology at UCSF and one of the leaders of the study. "So we were actually surprised when we didn't see any evidence of it in our adult samples."
Neurons are the oddly shaped cells that process and transmit information in our brain. Arturo Alvarez-Buylla, the principal investigator of the study, described them as the semiconductors of the brain.
The vast majority of neurons are generated during fetal development, but scientists have shown that in some regions of the brain, new neurons can continue to be made in adult animals.
"It is really a feat of biology," said Alvarez-Buylla. "The cell has to be born, then migrate and integrate into the tissue, make new extensions to connect with other cells, and then it has to contribute to the brain function."
Although this process has been well studied in mice, rats and canaries among other animals, only a handful of studies have sought to discover if neurogenesis also occurs in people after childhood.
"It's tricky," Paredes said. "It's hard to study human brain tissue, not only to get the samples, but to know how to analyze them and have confidence in the result."
The samples used in this work were collected from hospitals in China, Spain, Los Angeles and San Francisco. Most of the brain tissue came from people who had just died, but 22 samples came from brain operations that were performed on living people as a treatment for epilepsy.
"In those cases we were able to get the tissue very quickly, preserve them in the best way possible and then analyze them with less concern for degradation," Paredes said.
Instead of looking for new neurons themselves, the authors analyzed their tissue samples for combinations of proteins that are associated both with young neurons and with the stem cells that would make new neurons.
To make sure there was no mistake with their detection method, the authors looked to see if they could find evidence of new neuron growth in the brain tissue of fetuses, where they were certain that new neurons were developing. And indeed, when they looked at the fetal hippocampus, they were able to see that it was filled with young neurons.
"So in that case, we thought, we definitely have the tools to see them," Paredes said.
Next they wondered if perhaps their methods were only capable of detecting neurogenesis in young brains, and not in the brains of adults. To see if that was the case they analyzed two post-mortem autopsy samples and looked for evidence of young neurons in another region of the brain that is known to produce new neurons into childhood. There, the authors did find rare examples of young neurons, but very few.
"That showed us that we do have the ability to detect them, even in adult cases as well," Paredes said.
After they were convinced that there was nothing wrong with their detection technique, the authors set about making sense of their data.
Their research had shown that there are significantly fewer immature neurons in the 1-year-old brain, compared to earlier stages of life. In addition, the oldest sample where they still saw evidence of young neurons came from a 13-year-old."
"This was a very extensive and detailed undertaking that is critical to the field," Sahay said.
While the authors have some thoughts as to why previous work on neurogenesis in humans do not agree with their findings, they also say that more work needs to be done to understand exactly what is going on in the human brain.
"There are only a handful of studies out there that have already attempted to look at this, and they came to wildly different conclusions," said Shawn Sorrell, a senior researcher in Alvarez-Buylla's lab who co-led the work. "We felt there was room for another voice on this and another set of data that could provide more clues to what is happening in humans."
He added that reconciling all the various findings is "part of the scientific enterprise."
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One of the reasons scientists are so interested in the possibility of adult human neurogenesis is that it suggests one way that the human brain might repair itself, said Alvarez-Buylla.
"A new neuron made in the brain would be an incredible tool to fix brains," he said.
But both the authors and other experts in the field say the new work is no reason to give up on the dream that neurogenesis could one day be harnessed to help humans.
"The takeaway is not that it is pointless to study neurogenesis," Sahay said. "Neuroscience is replete with examples of how to restore plasticity in the brain."
Perhaps future work will reveal what mechanisms animals are using to generate new neurons into adulthood, as well as how the human brain might be taught to master this challenging feat.