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Brain tissue samples from people of all ages suggest we stop growing new neurons in our early teens

Brain tissue samples from people of all ages suggest we stop growing new neurons in our early teens
Two brain samples reveal how neurogenesis changes over time. At left, a sample from an infant brain reveals young neurons (green) in the hippocampus alongside more mature neurons (red), At right, mature neurons predominate in an adult human hippocampus. (Ken Probst and Sorrells et al.)

It was a tantalizing notion that seemed to be confirmed by a smattering of scientific studies — that the human brain could add more neurons to its circuitry even after it had reached maturity.

But new research suggests that may not be the case after all.

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The findings, published Wednesday in Nature, is sure to make a splash, said Amar Sahay, a professor at the Harvard Stem Cell Institute who was not involved in the work.

“But that’s science,” Sahay 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 a process known as neurogenesis.

A small number of papers had indicated that humans also possessed this capability, specifically in an interior region of the brain known as the hippocampus, which is associated with memory.

A team from UC San Francisco had hoped to see evidence of this neurogenesis in action.

Team members examined brain tissue samples collected from 59 human subjects who ranged in age from a 14-week-old fetus to a 77-year-old man. But they couldn’t find what they were looking for.

Instead, their research revealed that neurogenesis in humans drops off considerably 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.

“We went into this work thinking we were going to find evidence of neurogenesis because other groups did,” said Dr. 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 the brain. Arturo Alvarez-Buylla, the principal investigator of the study, described them as the brain’s semiconductors.

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,” Alvarez-Buylla said. “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 animals, only a handful of efforts 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.”

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The samples used in this work were collected from hospitals in San Francisco, Los Angeles, China and Spain. Most of the brain tissue was recovered from people who had just died, but 22 samples were gathered from living people who were being operated on 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 searched for combinations of proteins that are associated with young neurons or with the stem cells that would become new neurons.

To make sure there was no mistake with their detection method, the authors tried to find evidence of new neuron growth in fetal brain tissue, 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 checked to make sure their methods were capable of detecting neurogenesis in the brains of adults.

To see if that was the case, they analyzed two autopsy samples from adults 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 examples of young neurons, but very few.

“That showed us that we do have the ability to detect them, even in adult cases,” Paredes said.

After they were convinced that there was nothing wrong with their detection technique, the team members set about making sense of their data.

Their research revealed 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.

The authors shared some thoughts as to why their findings are at odds with previous work on neurogenesis in humans. For example, they wrote that detection techniques used by other teams to reveal young neurons may be less reliable than previously thought.

But they also said 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 Sorrells, 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.”

One of the reasons scientists are so interested in the possibility of adult human neurogenesis is that it suggests a way that the human brain might repair itself, Alvarez-Buylla said.

“A new neuron made in the brain would be an incredible tool to fix brains,” he said.

The study authors and other experts in the field agreed that there’s no reason to give up on the dream that neurogensis 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, scientists said.

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2:35 p.m.: This story has been updated with additional information throughout.

This story was originally published at 10:30 a.m.

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