A new study published this week in Cell Stem Cell is set to further stoke the debate over whether our brain can actually grow back neurons as we age. The research found that people, even into their golden years, are regenerating their stock of neurons right up until the point of death - seemingly contradicting the results of a major study released just last month.
Researchers from Columbia University studied brains donated soon after death from 26 people, ranging from ages 14 to 79. They specifically looked at the dentate gyrus, a part of the hippocampus (the region of the brain that helps coordinate our capacity for memory) where research in mice and humans has long suggested new neurons are regularly born. They found evidence of new neuron growth, or neurogenesis, in all the brains, as well as evidence of angiogenesis, or the formation of new blood vessels. More than that, they also found that age doesn't seem to slow down this growth.
"So people who were older and people who were younger had the overall same amount of new neurons and progenitor cells, somewhere around thousands," lead author Maura Boldrini, a neurobiologist at Columbia, told Gizmodo.
Older brains did seem to have a smaller pool of stem cells, reduced angiogenesis, and less neuroplasticity (the ability for neurons to make new connections with other neurons) than those younger, however.
Boldrini is no stranger to the roiling debate over neurogenesis. She recalls going through school being taught that the adult human brain simply doesn't grow back. But when studies began finding that new neurons grow all the time in animals such as mice and songbirds, starting in the 1980s, Boldrini was among the many scientists inspired to test out whether the same was true in humans.
She and other researchers have conducted studies throughout the years indicating that it does happen in adults. She's also collaborated on research that's suggested a lack of neuron growth might play a role in mental health conditions like depression or suicidal ideation, and that certain treatments like antidepressants can help start the process back up.
However, a study in Nature last month provided a sharp rebuttal to the theory. The team, which included a researcher who once helped prove animal neurogenesis was real, analysed samples of the hippocampus donated by 59 people, both living and dead, and found no evidence of neuron growth in human brains past the age of 13.
Boldrini insists that her team's findings aren't meant to attack the credibility of the Nature researchers. "I know Buylla's group," she said, referencing University of California San Francisco researcher Arturo Alvarez-Buylla, who was the senior author of the study. "We know each other, we've been at the same meetings. It's a fantastic group."
Instead, she said the differing results might come down to the brains each team looked at.
"They had brains from four different places around the world, like Asia, Europe, the US. And they said they analysed three to five sections of the hippocampus. So they didn't have the whole hippocampus, of course," she said. "These brains were also treated with different chemicals, and they were comparing them to each other. And each of these chemicals that are used to preserve the brain can affect the cells that you see - it's like comparing a roasted chicken with a chicken that's been fried."
The brains analysed in the current study were from a single collection maintained by Boldrini's team, each preserved the same way within 24 hours of death, all with no identifiable health problems, Boldrini noted. Meanwhile, the Nature study got some samples from people who were given surgery to treat epilepsy, as well as from brains collected up to 48 hours after death. These are factors that could have influenced their results, she said.
"We have the whole brain donated by the family. And that's crucial, actually, to be able to estimate the total number of cells you're interested in looking at," she also explained. "That's impossible to do if you only have pieces of the brain."
Far from being just an arcane fight in the pages of stuffy journals, Boldrini said it's important to know for sure whether the brain really can regrow.
"If the neurons are there, then we have the potential to learn how things work when there's a pathology," she said. "For instance, we studied healthy ageing brains. But we could compare this data with the brains of people who had Alzheimer's disease. We can then try to figure out the mechanisms that regulate the maturation of these neurons. So if things go wrong, we can actually manipulate them and cure people."
Boldrini said the best way forward to settle the debate is for researchers to collaborate more together and conduct easily reproducible research on a wider but similarly collected variety of donated brains. She points to collection efforts such as the Brain Initiative begun in 2013 by the National Institutes of Health as a good example.
"We need to be studying the same material," she said. "That's fundamental."
Update: The authors of the Nature study issued this statement in response:
"While the new study by Boldrini et al offers interesting evidence of declining blood vessel growth in the adult hippocampus, we dispute the interpretation of their cellular staining experiments as evidence of new neurons in the adult brain.
Identifying new neurons is technically challenging - in our own recent study we made similar observations to what Boldrini et al report, but after performing extensive additional analysis of the shape and other characteristics of the cells in question, including electron microscopy and gene expression, we determined that these cells were not in fact young neurons or neural progenitors but different types of cells altogether.
For now, we do not think this new study challenges what we have concluded from our own recently published observations: If neurogenesis continues in the adult human hippocampus, it is an extremely rare phenomenon."