Your brain can’t make new cells after childhood. What you have in your noggin once you’ve emerged from puberty is all you’ll get for the rest of your life.
Or is it?
It depends who you ask.
Research published today in Cell Stem Cell suggests that a healthy person, even in their 70s, will keep churning out new brain cells — a process called neurogenesis — at a rate comparable to a teenaged brain.
But just last month, a paper in Nature claimed the opposite: that after hitting adulthood, neuron production grinds to a halt.
How can two studies searching for the same thing reach opposite conclusions?
Devil in the detail
These two papers, and others like them, focus on the hippocampus: a curved structure, a few centimetres long, tucked away deep in the brain. Among other things, it’s responsible for creating new memories.
Specifically, both research teams concentrated on an area where the hippocampus receives a lot of inbound information, called the dentate gyrus. It’s one of the few brain areas where neurogenesis was found in adult rats.
Each group followed a different imaging protocol. The way brain tissue is preserved and stained contributes to how well — or not — the cells show up.
So that’s one possible source of the discrepancy: one staining system might not be sensitive enough, while another might work too well, generating background noise and false positives.
To kick off the staining protocol, most neuroscientists drop fresh brain tissue into chemicals to “fix” it, University of Sydney neuropathologist Greg Sutherland said.
The Cell Stem Cell study, led by scientists at Columbia University in New York, flash-froze tissue samples first. This, Dr Sutherland said, is “quite distinct from how most people do it”. So that’s another difference.
Then there’s the brains themselves — and the people who donated them to science. The Columbia study counted newly formed neurons in the entire hippocampus of 28 healthy donors, aged from 14 to 79, shortly after they died.
The Nature paper, which was done in San Francisco, also assessed post-mortem brain tissue, alongside some samples taken directly from patients with epilepsy who were having brain surgery.
From a total of 59 different brains, which ranged from foetuses to a 77-year-old, the San Francisco team detected plenty of new cell growth in the youngest brains — but none at all in people over the age of 18.
The problem with people
Most research into neurogenesis, unsurprisingly, has been in animals, according to Lachlan Thompson, a neurobiologist at the Florey Institute of Neuroscience and Mental Health in Melbourne.
Columbia University neurobiologist Maura Boldrini, lead author of the Cell Stem Cell paper, said neurogenesis “declines pretty sharply after middle age in mice and also in non-human primates”.
But, of course, these animals aren’t human. And even though they share much of our genome, they’re not identical to us.
And researchers can’t crack open someone’s skull, burrow through the wrinkly outer brain layers, peer at the hippocampus with a microscope and close the head up again.
Instead, they must wait for people to die — and locating brain stem cells in post-mortem hippocampi “is notoriously difficult”, Dr Thompson said.
Fresh is best, so scientists must get their hands on the brain tissue and preserve it within just a few hours.
Even if all the samples are well preserved, there are lots of factors that can affect neurogenesis. Some anti-depressants, for instance, boost new neuron growth; stress can decrease it.
And even with a vast and varied swag of donor brain tissue, these studies are just a snapshot of the brain’s cellular structure at the time of death — they can’t see how it changes over time, Dr Thompson said.
Dr Boldrini agrees: “These are numbers at the time of death. We don’t know how long they last.”
Why all the fuss over new brain cells?
New cell growth in the brain has been a controversial topic for decades.
Until the 1990s, it was generally assumed that humans were born with all the brain cells they’ll ever have.
But slowly, new insights started to chip away at the dogma. A key moment came in 1998 with a human post-mortem study led by American neurobiologist Fred Gage.
In a paper called Neurogenesis in the adult human hippocampus, Professor Gage and his team examined the brain of patients who’d been injected with a marker that is only absorbed by dividing cells. Sure enough, they found evidence that brain cells divided and matured in the full-grown adult hippocampus.
The results, they wrote, “further indicate that the human hippocampus retains its ability to generate neurons throughout life”.
Newborn neurons, which arise from neural stem cells, worm their way into the dentate gyrus where they extend fibres called axons to communicate with other neurons.
If scientists can harness this process, and stimulate stem cells to get dividing and proliferating, it may provide hope for patients with neurodegenerative disorders such as Alzheimer’s disease, said Bryce Vissel, a neuroscientist at the University of Technology Sydney.
One of the brain areas first destroyed in Alzheimer’s is the hippocampus — it’s why one of the hallmark symptoms of the disease is memory decline.
So … who’s right?
It’s safe to say the question of adult neurogenesis is still open. In relation to the Columbia study, Dr Thompson was “cautious about overstating the results”.
Dr Sutherland agrees. In 2013, his lab found signs of neurogenesis in brains of very young children, but “once we got to three or four years of age, we found none”, he said.
He’d like to see the Columbia methodology used on brain tissue from very young children and newborns.
Meanwhile, new imaging techniques might offer some hope of a definitive answer.
Only in February this year, researchers managed to spy neural stem cells creating neurons in a mouse brain over a two-month period.
Optogenetics, a technique that switches brain cells on and off using light, could be adapted for imaging. One day, it may be possible to see neurogenesis take place in a living human brain, he said.
In the meantime, the controversy will continue to bubble away.
“This story is still live,” Professor Vissel said.