Study casts doubt on whether adult brain’s memory-forming region makes new cells

In stark contrast to earlier findings, adults do not produce new nerve cells in a brain area important to memory and navigation, scientists conclude after scrutinizing 54 human brains spanning the age spectrum.

The finding is preliminary. But if confirmed, it would overturn the widely accepted and potentially powerful idea that in people, the memory-related hippocampus constantly churns out new neurons in adulthood. Adult brains showed no signs of such turnover in that region, researchers reported November 13 at a meeting of the Society for Neuroscience in Washington, D.C.

Previous studies in animals have hinted that boosting the birthrate of new neurons, a process called neurogenesis, in the hippocampus might enhance memory or learning abilities, combat depression and even stave off the mental decline that comes with dementia and old age (SN: 9/27/08, p. 5). In rodents, exercise, enriched environments and other tweaks can boost hippocampal neurogenesis — and more excitingly, memory performance. But the new study may temper those ambitions, at least for people.

Researchers studied 54 human brain samples that ranged from fetal stages to age 77, acquired either postmortem or during brain surgery. These samples were cut into thin slices and probed with molecular tools that can signal dividing or young cells, both of which are signs that nerve cells are being born. 

As expected, fetal and infant samples showed evidence of both dividing cells that give rise to new neurons and young neurons themselves in the hippocampus. But with age, these numbers declined. In brain tissue from a 13-year-old, the researchers spotted only a handful of young neurons. And in adults, there were none.

“We were unable to detect young neurons in adult human hippocampus,” study coauthor Shawn Sorrells of the University of California, San Francisco said in his presentation.

The researchers also looked for physical signs of dividing cells and young neurons, such as small, elongated nuclei, using electron microscopy and light microscopy. Again, there was no evidence of newborn neurons in adults, Sorrells said in his presentation. (Because the results have been submitted for potential publication in a journal, Sorrells declined to comment for this story.)

That absence of young hippocampal neurons conflicts with some earlier research. A definitive answer has eluded scientists in part because there’s no easy way to study these cells in living people. Several of the earlier studies relied on unusual circumstances to spot cells born in adulthood.

A landmark study, published in Nature Medicine in 1998, found newborn neurons in the hippocampi of people who, as part of their cancer treatment, had been dosed with an imaging molecule called BrdU that gets incorporated into the DNA of newly formed neurons.

A different approach, published in 2013 in Cell, led to the same conclusion. By looking at people exposed to radioactive carbon released during Cold War bomb testing as adults, Jonas Frisén and colleagues found a surprisingly large number of newborn hippocampal cells — an estimated 700 new cells per day in each hippocampus (brains have one hippocampus on each side).

The methods used to study tissue from people after they’ve died can be finicky, particularly that from older people. Molecular markers of neurogenesis in adult brain tissue can be difficult to see, making the method “extremely challenging,” says Frisén, of the Karolinska Institute in Stockholm.

It’s also possible that the birth rate of neurons varies widely from person to person. “There are huge differences between different mouse strains,” Frisén says, and it’s not unreasonable that similar differences might exist in people. In the new study, the subjects’ health could have declined before their deaths, reducing neurogenesis at the very end of their lives.  

Experts say the preliminary study is not the last word. “I would love to see more data,” says Gerd Kempermann of Technische Universität Dresden in Germany. In the meantime, the body of evidence in favor of human neurogenesis in the hippocampus, including results from his lab, is quite strong, Kempermann says.

“I am convinced enough that an abstract at a meeting claiming otherwise does not shake up my concept,” Kempermann says. But he thinks it will be valuable to explore other explanations for the results, even if they don’t overturn the idea of human hippocampus neurogenesis. “Let’s be open and wait,” he says.