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The Brain May Actually Keep Generating New Cells Well Into Old Age

An analysis of 58 brain samples found that neurogenesis declines over time and is particularly poor among those with Alzheimer’s

Immature (red) and mature (blue) neurons in the hippocampus of a 68 year-old (Elena P. Moreno-Jiménez)
smithsonian.com

Scientists have long been divided over whether neurogenesis—a process involving the growth of new neurons—continues into adulthood. Last year, a controversial study published in the journal Nature posited that humans stop generating new cells in the learning- and memory-centered hippocampus region long before reaching adolescence. Now, research published in Nature Medicine shifts the debate back in favor of late-in-life neurogenesis: As Sharon Begley reports for STAT, the latest findings suggest humans are actually capable of producing fresh cells well into their 90s.

Expanding on the Madrid-based team’s paper, BBC News’ James Gallagher explains that an analysis of 58 brains belonging to recently-deceased individuals aged 43 to 97 revealed a discernible decline in neurogenesis over time. This drop in new cell production was particularly exacerbated among 45 test subjects (aged 52 to 97) who had been diagnosed with Alzheimer’s disease prior to their deaths, Ian Sample writes for the Guardian, but was evident at less severe levels among the 13 brain donors (aged 43 to 87) who were neurologically healthy at the time of their deaths.

The fact that new neurons were being made at all bodes well for researchers hoping to capitalize on the manifold benefits of hippocampus cell creation. As Karen Weintraub points out for Scientific American, such continued growth could help those working to recover from depression and post-traumatic stress disorder, or perhaps even delay the onset of Alzheimer’s disease.

“I believe we [are] generating new neurons as long as we need to learn new things,” senior study author María Llorens-Martín, a neuroscientist at the Autonomous University of Madrid, tells BBC News’ Gallagher. "And that occurs during every single second of our life."

According to Science magazine’s Emily Underwood, the main difference between the new research and the 2018 paper discounting adulthood neurogenesis is the method used to preserve donated brain tissue. For the older study, scientists examined 59 samples, some of which were drawn from brain banks where they had been kept in fixative paraformaldehyde for an extended period of time. This paraformaldehyde can turn cells into gel, Llorens-Martín explains to Underwood, thereby discouraging binding with the doublecortin (DCX) protein that researchers rely on to gauge neuron development.

Crucially, the team behind the new study found that levels of DCX in brain tissue experience a sharp decline within just 48 hours of being immersed in paraformaldehyde. Wait six months, Llorens-Martín observes, and neuron detection becomes “almost impossible.”

As Laura Sanders notes for Science News, the Madrid researchers relied on donated brain tissue processed within 10 hours of death and soaked in preservatives for no longer than 24 hours. The youngest test subject—a neurologically healthy 43-year-old—yielded around 42,000 “immature” neurons per square millimeter of tissue, Science’s Underwood reports. Comparatively, the oldest donors had some 30 percent fewer newly produced neurons. Those with Alzheimer’s, in turn, had 30 percent fewer immature neurons than healthy donors of the same age. Michael Bonaguidi, a stem cell biologist at the University of Southern California who was not involved in the study, tells Scientific American’s Weintraub the paper is a “technical tour de force” that overcomes the issues raised by last year’s study.

But Shawn Sorrells, a neuroscientist at the University of Pittsburgh in Pennsylvania who co-authored the 2018 paper, tells Underwood he and his colleagues “did not find the evidence for ongoing production of new neurons … convincing.” It’s possible, he says, that the “immature” neurons spotted by the team were actually present since childhood, as DCX also shows up in mature cells.

It’s unlikely this latest study will settle the debate once and for all, but the paper does hold promising implications for Alzheimer’s treatment. If neuroscientists can figure out a way to detect newly-formed cells in living humans, they may be able to diagnose the disease in its earliest stages.

“This could not be applied to advanced stages of Alzheimer’s disease,” Llorens-Martín concludes to Weintraub. “But if we could act at earlier stages where mobility is not yet compromised, who knows, maybe we could slow down or prevent some of the loss of plasticity [in the brain].”

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