At the beginning of the 20th century, Santiago Ramón y Cajal, often called “the father of modern neuroscience,” made it clear: In adults, “the nerve paths are something fixed, ended, and immutable. Everything may die, nothing may be regenerated,” he wrote.
The inability of adults to produce new neurons was pretty much the central dogma of neuroscience until the 1960s. But as with a lot of fathers in that decade, a younger person challenged Ramón y Cajal’s decree.
In 1962, Josef Altman, an American biologist, published a paper in the journal Science entitled “Are New Neurons Formed in the Brains of Adult Mammals?” The answer was that they very well might be. In subsequent years, the work of Altman and other researchers clearly demonstrated the activity of neural stem cells (the cells that make new neurons) in adult mammals.
However, the old dogma didn’t die without a fight. Many, if not most, neuroscientists were skeptical, and a few studies raised questions about whether adult humans made new brain cells.
Creating New Brain Cells
Over the past few years, the evidence has accumulated in favor of neural stem cell existence and prolonged activity in the human adult brain. Recent studies have helped shed light on the debate, with many using single-cell RNA sequencing and other advanced technologies to look at parts of the brain, such as the hippocampus and the subventricular zone.
Those studies provide strong evidence for the existence and activity of neural stem cells in humans, explains Tyson Ruetz, a scientist who specializes in the study of aging and regenerative medicine.
But what are these new cells doing? While much of the evidence is based on studies in mice, says Ruetz, the studies are showing that these cells are important in memory formation and in helping to repair damage to the brain caused by traumatic brain injury and stroke, and their activity is affected by Parkinson’s disease and Alzheimer’s disease.
“In those contexts,” Ruetz says, “there is a lot of activity, thousands or even tens of thousands of newborn neurons helping to repair those damaged sites.” Or at least they do when the brain damage happens in young mice.
However, as mammals age, our neural stem cells become dormant or “sleepy,” as Ruetz puts it. They don’t wake up when the brain is injured. It’s as if the alarm at the fire station is no longer working.
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Potential Therapies
Ruetz and colleagues at Stanford University wanted to know if there are genes that are overactive in the aging brain, causing aging neural stem cells to remain dormant. Using CRISPR-Cas9 gene-editing tools to knock out each of 23,000 genes in old mice, they found more than 300 genes that, when silenced, resulted in restored neural stem cell function.
Taking a closer look at these genes, they discovered that they had knocked out a gene for a protein that transports glucose: glucose transporter type four, also known as GLUT4. This was particularly interesting because, in the context of Alzheimer’s disease, the brains of Alzheimer’s patients have severely disrupted glucose signaling, Ruetz explains.
“We dug deeper, and we found some really interesting metabolic changes that happened in old neural stem cells. If we knocked out just the glucose transporter type four, we saw more than a two-fold improvement in neural stem cell activity in the brain in old mice,” says Ruetz. They published their results this October in Nature.
Impaired glucose signaling in patients with Alzheimer’s and with dementia more generally have led some to call dementia “type 3 diabetes,” and Ruetz’s research supports that idea.
“It’s possible that severely disrupted insulin glucose signaling is having profound effects on the ability of the brain to repair and regenerate itself, in part by suppressing neural stem cell activity,” says Ruetz.
Some clinical trials have shown that administering insulin through the nasal passages results in more efficient delivery of insulin to the brain, and those trials have demonstrated some improvement in people with Alzheimer’s dementia, further supporting the idea.
Ruetz recently co-founded ReneuBio, a company that is developing therapies that would make use of these findings, and those of others in the field, to boost the regenerative capacities of the aging brain. Meanwhile, a healthy diet and plenty of exercise — you knew this was coming — may be your best bets for nurturing those baby brain cells. Ruetz also recommends keeping the brain active with enriched environments and challenging new tasks.
“That can lead to some resiliency throughout aging,” he says, “long before you need a pharmacological intervention.”
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Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
Avery Hurt is a freelance science journalist. In addition to writing for Discover, she writes regularly for a variety of outlets, both print and online, including National Geographic, Science News Explores, Medscape, and WebMD. She’s the author of Bullet With Your Name on It: What You Will Probably Die From and What You Can Do About It, Clerisy Press 2007, as well as several books for young readers. Avery got her start in journalism while attending university, writing for the school newspaper and editing the student non-fiction magazine. Though she writes about all areas of science, she is particularly interested in neuroscience, the science of consciousness, and AI–interests she developed while earning a degree in philosophy.
