For seven years, molecular biologist and his colleagues played what felt like the world鈥檚 most exhausting game of hide-and-seek.
Yet instead of peeking around doors or under beds, they were examining brain tissue in a lab at the Karolinska Institute in Sweden, looking for something that had long evaded neuroscientists: concrete proof that the adult brain can form new neurons via a process called neurogenesis. 女生小视频s have spent decades debating whether this is possible. As soon as one paper turned up positive clues, another would yield nothing at all.
But it seems the search may finally be over. A slew of new findings, including those from Dumitru and his team, have revealed near-certain evidence that adult neurogenesis occurs in the human hippocampus, part of the brain central to learning and memory. The discovery is forcing us to rethink long-held assumptions about our most indispensable organ, from how it functions to how it changes with age.
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Even more exciting is the potential neurogenesis holds for brain regeneration. Some of our most devastating medical conditions, including , stroke and (ALS), involve neurons dying at massive scale. If the brain is capable of replacing some of those lost neurons, we may be able to harness and enhance that ability, stimulating neurogenesis to help treat neurological conditions that are currently incurable.
鈥淭o many of us, we think the question is no longer whether it exists or not,鈥� says neuroscientist at the University of Pennsylvania. 鈥淚t鈥檚, how can we take advantage of that?鈥�
Neurons are the brain鈥檚 , transmitting the signals that underpin our most basic functions, from moving and talking to thinking and dreaming. They form when a stem cell 鈥� which can morph into other cell types 鈥� transforms into a 鈥減arent鈥� progenitor cell, which then births an immature neuron that eventually matures.
女生小视频s long believed this process played out only during development in the womb and, to a lesser degree, during childhood and adolescence. In other words, humans were born with essentially all the neurons they would ever have. The brain would change in many ways over one鈥檚 lifetime 鈥� forming new connections between neurons and those that were no longer necessary 鈥� but it wasn鈥檛 going to get a windfall of new neurons. Or at least, so we thought.
In the early 1960s, Joseph Altman, a biologist at the Massachusetts Institute of Technology, went against the grain by looking for signs of neurogenesis in adult rats. He injected the animals with , then identified cells bearing it in the rodents鈥� brains, revealing what appeared to be freshly generated neurons.
But the finding was by the neuroscience community. The idea that adult neurogenesis was impossible 鈥渉ad really been embedded within the scientific literature鈥�, says , a neuroscientist at the Salk Institute for Biological Studies in California.
Altman was apparently undeterred, replicating his findings in . Other researchers eventually joined in, finding adult neurogenesis in species such as and , and discovering that it seemed to play a role in learning and memory 鈥� , for instance.
But whether human brains also pump out new neurons remained an open question. You can鈥檛 ethically crack open a living person鈥檚 skull and dig around in their brain tissue.
Gage and his colleagues found an ingenious workaround to that problem. In the 1990s, some people being treated for cancer received injections of a chemical called BrdU, which flagged dividing cells so that doctors could monitor disease spread. When five such patients had died, Gage and his colleagues were able to autopsy their brains. Lo and behold, they 鈥� a sign of neurogenesis.
The trouble is that BrdU can sometimes , not necessarily division. And subsequent studies that used different markers yielded results all over the map. Some showed ; others, that the adult hippocampus adds 700 new neurons every single day, on a par with that of a much younger brain.
So, Song and his colleagues pioneered a different approach. Instead of looking for immature neurons with just one or two markers, they analysed the full genetic profile of individual brain cells, searching for the genetic characteristics of freshly generated cells. They discovered immature neurons in people who had died across all stages of life, even up to age 92.
But spotting a young neuron still isn鈥檛 enough to prove the adult brain is generating new ones. Neurons can linger in an immature state for a long time, . These Peter Pans of the brain aren鈥檛 necessarily created in adulthood; they just aren鈥檛 growing up.
The real challenge in proving adult neurogenesis occurs was to capture each stage of the process 鈥� and one remained elusive. 鈥淣obody had identified the proliferating progenitors,鈥� says Dumitru. 鈥淭hey could identify immature neurons, they could identify maybe stem cells 鈥� so the cells that are at the beginning and end of the trajectory 鈥� but nobody identified the proliferating ones.鈥�
To identify these cells, which actually birth new neurons, Dumitru and his colleagues genetically analysed roughly 400,000 brain cells from the hippocampi of people who had died between infancy and adulthood. They used a machine learning model 鈥� a type of artificial intelligence 鈥� to pinpoint genetic patterns that resembled those seen in progenitors from animals and developing infants.
The researchers almost couldn鈥檛 believe it when they spotted the first few progenitors. 鈥淚t was so difficult to convince ourselves,鈥� says team member , a molecular biologist also at the Karolinska Institute.
But after years of testing and re-testing, they finally felt confident their search was over. They found only about 鈥� and they weren鈥檛 present in all the brains sampled. But by finding any at all, 鈥渨e showed that there is active neurogenesis鈥� in the hippocampus, says Dumitru. 鈥淭hat cannot be contested.鈥�
Except that, well, some scientists still do. Developmental neurobiologist at the University of California, San Francisco, isn鈥檛 convinced that machine learning models can reliably categorise cell types. He says the only way to know for certain that adult neurogenesis happens would be to track a stem cell as it transforms into a neuron 鈥� a nearly impossible task to do in a living human.
But sceptics like Alvarez-Buylla are increasingly finding themselves outside a coalescing consensus. At least related to adult neurogenesis are now under way. 鈥淚t鈥檚 there,鈥� says , a neuroscientist at King鈥檚 College London. 鈥淭he new debate is, what is it for?鈥�
One of the first clues to answering that question comes from the fact that adult neurogenesis appears almost exclusive to the hippocampus, the brain鈥檚 headquarters of learning and memory. This region is highly plastic, meaning it can easily reorganise itself and form new connections, helping us to take in and remember new information.
In a study from earlier this year, neuroscientist at the University of Illinois College of Medicine and her colleagues found that neurogenesis may play a role in this process. They examined post-mortem hippocampus samples from adults who had 础濒锄丑别颈尘别谤鈥檚 and adults without cognitive impairments, including 鈥渟uperagers鈥� 鈥� people in their eighties or older who had outperformed younger adults on a memory test. On average, superagers had in their hippocampus as adults without cognitive impairments. People with 础濒锄丑别颈尘别谤鈥檚 had almost none at all.
The finding suggests that neurogenesis is closely linked with cognition and may even stave off its decline. Some of the superagers with an abundance of immature neurons also showed signs of 础濒锄丑别颈尘别谤鈥檚 in their brains, including the condition鈥檚 characteristic plaques and tangles. It is possible that enhanced neurogenesis allows the brain to bypass or overcome what would otherwise contribute to cognitive decline, says Lazarov.
Several studies within the past year have also found neurogenesis is impaired in other conditions like and . The latter finding comes from the lab of , a neuroscientist at Columbia University, New York, who has spent the past 20 years trying to understand the connection between neurogenesis and depression.
His interest began after coming across a study that showed . Curious about whether this could explain how antidepressants work, Hen ran a follow-up experiment and found that if he manipulated rodents鈥� brains to stop producing new neurons, they also stopped responding to antidepressants. Hen was hooked and has been investigating the link ever since.
He and his colleagues have shown that, at least in animals, hippocampal neurogenesis seems 鈥� the ability to distinguish between different objects, situations and emotions and remember them appropriately. This process is impaired in depression, as well as other psychiatric conditions in which neurogenesis may go awry, such as and . It may explain why people with depression can tend to overgeneralise, for example, interpreting one bad day as evidence that things will always be bad, says Hen.
Like 础濒锄丑别颈尘别谤鈥檚 disease, these mental health conditions are also associated with smaller hippocampal volumes. While there are probably multiple factors that contribute to this, it is possible that impaired neurogenesis is one of them, says Hen.
Finding a way to stimulate neurogenesis could, therefore, be a promising treatment approach. Several studies have indicated that already available medications, such as antidepressants and the diabetes medication , could stoke neurogenesis.
But there could be more advanced ways of manipulating the process. For instance, if we can pinpoint why superagers have increased neurogenesis, and why it seems to be protective, we could potentially develop therapies that mimic these effects. 鈥淲e might be able to provide some kind of shield [against cognitive decline],鈥� says Lazarov.
Harnessing neurogenesis could even treat conditions it isn鈥檛 directly involved in, such as traumatic brain injury or stroke. A 2025 study showed that transplanting neural progenitor cells into the brains of mice after a stroke and helped the animals regain lost movement.
Still, it will take years to determine whether any neurogenesis interventions work, and even longer to bring them to market if they do. Song and his team are trying to speed up the process by developing miniature models, or organoids, of the human hippocampus. Because these organoids capture what happens in the living human brain more accurately than animal models, they could make it easier to identify therapies that boost neurogenesis, says Song. Other researchers are trying to to measure neurogenesis in living people, with similar goals.
There may be simpler interventions, too. 鈥淟ifestyle is an easy way of modulating, potentially, neurogenesis,鈥� says Thuret.
Research has long shown that neurogenesis increases in rats when they are mentally stimulated, such as by having roommates or fun toys in their cages; people may similarly benefit from enriching activities like socialising or learning a new skill.
Exercise also shows promise, at least in rodents. Gage and his colleagues found that when adult rats run on exercise wheels, they produce more immature neurons than sedentary rodents. They also do a better job navigating a maze, signifying enhanced cognitive performance.
Thuret was curious whether the same could be true for humans. So earlier this year, she and her team exposed human hippocampal stem cells to blood serum taken from adults who had completed a three-month exercise programme and those who hadn鈥檛. But instead of stoking neurogenesis, blood from the exercisers actually ready to become new neurons.
Thuret is still trying to unravel what this means. But given that it is well established that exercise benefits brain health, it may not necessarily be a negative outcome. It is possible that physical activity helps regulate the pace at which stem cells transform into neurons, reserving some for future development, she says.
It is intuitive to think that if impaired neurogenesis is bad, cranking it up to 11 would be good. But too much neurogenesis could backfire, says Thuret. Cancer, a disease of unchecked cell growth, is a prime example of how more isn鈥檛 always better when it comes to the human body.
This is just one reason why indiscriminately turning up neurogenesis probably isn鈥檛 a viable treatment option. It is more likely that therapies of the future will be targeted, tweaking neurogenesis in different ways and to different levels to treat various conditions, rather than having an across-the-board fix, says Thuret.
Plus, as far as researchers have been able to tell, neurogenesis is mostly confined to the hippocampus. Many cognitive and psychiatric symptoms originate there, but not all of them. For example, a completely different brain region mediates anhedonia 鈥� the inability to feel joy, which is a hallmark of depression. 鈥淚 don鈥檛 think that a drug that stimulates neurogenesis is going to cure anhedonia,鈥� says Hen. 鈥淭he medicine of the future is probably going to be a medicine where we use multiple drugs, each one targeting specific symptoms.鈥�
Unless, of course, neurogenesis isn鈥檛 limited to the hippocampus at all.
After finding progenitor cells in the hippocampus, Dumitru, Paterlini and their colleagues didn鈥檛 celebrate for long. Instead, they embarked on a new search, turning their attention to the subventricular zone, another part of the brain that some studies suggest . The work is in early stages, says Dumitru, but already they have spotted signs of progenitor cells in adult samples of this area 鈥� a new game of hide-and-seek has begun.
