Every day, the human hippocampus, a brain region involved in learning and memory, creates hundreds of new nerve cells — or so scientists thought. Now, results from a study could upend this long-standing idea. A team of researchers has found that the birth of neurons in this region seems to stop once we become adults.
A few years ago, the group looked at a well-preserved adult brain sample and spotted a few young neurons in several regions, but none in the hippocampus. So they decided to analyse hippocampus samples from dozens of donors, ranging from fetuses to people in their 60s and 70s. They concluded that the number of new hippocampal neurons starts to dwindle after birth and drops to near zero in adulthood. The results1, published in Nature on 7 March, are already raising controversy.
If confirmed, the findings would be a “huge blow” not only to scientists in the field, but also to people with certain brain disorders, says Ludwig Aigner, a neuroscientist at Paracelsus Medical University in Salzburg, Austria. This is because researchers had hoped to harness the brain’s ability to generate new neurons to treat neurodegenerative diseases such as Alzheimer’s and Parkinson’s, he says.
But Aigner and other neuroscientists are not fully persuaded by the findings, which contradict multiple lines of evidence that the hippocampus keeps producing neurons throughout a person’s life. “I wouldn’t close the books on [that],” says neuroscientist Heather Cameron of the US National Institute of Mental Health in Bethesda, Maryland.
Over the past 20 years, scientists have found that neuron creation in the hippocampi of people and animals such as rodents tends to decrease with age, but a few newborn nerve cells are present even in the oldest individuals2.
However, when a team of neuroscientists led by Arturo Alvarez-Buylla at the University of California, San Francisco, looked at thin hippocampus sections from 37 donors of different ages who had died in various ways, they spotted young neurons only in fetuses and children. The oldest sample in which the researchers still saw a few immature nerve cells belonged to a 13-year-old. “In the 18-year-old’s sample, we just don’t find any,” Alvarez-Buylla says.
But the findings are not so clear-cut, warns Gerd Kempermann, a neuroscientist at the Technical University of Dresden in Germany. Just because the scientists don’t see new neurons doesn’t mean they aren’t there, he says. Alvarez-Buylla and his colleagues used marker molecules to tag immature in brain samples that had been collected and prepared for analysis within 48 hours after an individual died. Whether these markers can reliably tag young neurons depends a lot on the quality of the tissue, which is influenced by how soon after death the samples are treated to keep them from decaying, Kempermann says.
The chemicals used to preserve and stabilize the tissue samples might also further prevent the markers from binding to their target cells, says neuroscientist Paul Lucassen at the University of Amsterdam. “It’s very hard to get these markers to work in these conditions.”
Although Alvarez-Buylla acknowledges the limitations of the study, he stands by its results. “We have done our homework and studied many samples of different ages,” he says. His team also analysed hippocampi from 22 patients treated for epilepsy, who had had parts of their brains removed and prepared for analysis on the spot. In those cases, the researchers didn’t find any young hippocampal neurons in people older than 11.
Some neuroscientists also caution that the physical and mental states of those who donated their brain for the analysis is important. “How much exercise did they have? Were they bedridden? Were they depressed because of the disease they had?” asks Fred Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, California. This is relevant, he says, because factors such as exercise, stress and disease influence the number of new hippocampal neurons generated3.
Despite these concerns, the study is likely to have some immediate effects on the field, says Sandrine Thuret, a neuroscientist at King’s College London. It could encourage others in the field to look for young neurons in the adult hippocampus, and push researchers to develop better markers for tracking the formation of neurons in living organisms, she says. At the very least, Thuret adds, the study’s conclusions are set to stir up debate.
See the related News & Views article, 'Questioning human neurogenesis'.