Even old brains can make new neurons, study suggests

Your body is constantly generating new cells. In your digestive tract, the colon’s lining turns over every five to seven days. Your red blood cells replace themselves every few weeks, skin cells about once a month. But certain organs are a big exception. Contrary to popular belief, we are not biological Theseus’ ships, reconstructing ourselves entirely from fresh building blocks every seven years. Most of your neurons, the cells that fast-track information across the brain, spine, and sensory organs, have the same lifespan as you do.

Until the late 20th century, the prevailing view in neuroscience was that, past childhood, humans stop making neurons, brain-wide. What we have in adolescence, is what we get, and all we can do is lose cells or reorganize them. However, the latest research adds to a mounting body of evidence finding that the timeline of neuron generation isn’t so clear-cut.

In at least two parts of the brain, a subset of neuroscientists believe that neurons may continue to form throughout life–the hippocampus and the ventral striatum. In the hippocampus, a critical brain region for learning and memory, new cells emerge in some people into late adulthood, according to a study published July 3 in the journal Science. The findings tip the scales in a still-active debate over how our brains continue to develop throughout life. A better understanding of adult neurogenesis (the formation of new neurons), and a firm answer to if and where it occurs, could help improve treatments for neurological diseases as well as normal aging. 

[ Related: Scientists mapped every neuron of an adult animal’s brain for the first time. ]

Are human brains uniquely static?

Past research in rodents, pigs, and monkeys has shown that neurogenesis does happen in these other mammals, throughout life. Birds do it too. Yet based on other noted structural and developmental differences in the human brain, some scientists argue that our species is unique and lacks the lifelong neurogenesis that might interrupt complex, streamlined brain function. (New neurons may sound great, but too much activity and connectivity can cause chaos.) And it’s difficult to get a clear answer. It’s a major technical challenge to pin down new brain cells in humans because you can’t readily see through living skulls at the cellular level. Researchers largely have to rely on scarce brain tissue collected via surgery on those with medical conditions like epilepsy or tissue donated by the deceased.

With this new study, “I think they used really strong tools,” Mercedes Paredes, a neurologist and developmental neuroscientist at University of California, San Francisco, tells Popular Science. Paredes was not involved in the research, but has previously found contrasting results in her own lab. The new work, she says, is a “good starting point” for applying novel methods to the brain and deciphering what types of cells are truly present. 

Other studies of potential adult neurogenesis have looked at protein and immune signatures in brain tissues to determine if, where, and how often new neurons are being formed. They’ve come to conflicting conclusions, with some (like Paredes’ 2018 work) failing to identify the cells that other researchers report seeing. There’ve also been a few studies that rely on carbon dating to ascertain the age of neurons, which find young cells in adults. However, none of these methods have, so far, reliably pinpointed the stem cells or progenitors capable of yielding fresh neurons–leaving room for doubt. 

Finding the ‘missing link’

The new study seems to address this previously unresolved point. It’s the “missing link” of neurogenesis, Jonas Frisén, senior study author and a developmental biologist and stem cell researcher at Karolinska Institutet in Stockholm, tells Popular Science.

To find that missing link, Frisén and his co-authors surveyed the scientific literature to compile a list of genes that are likely active in hippocampal neurogenesis. Then, they confirmed those gene markers (largely from animal studies) by comparing them to RNA sequences found in brain samples from six deceased, child and infant donors. Next, the team sequenced RNA from mitochondria in the brain tissue from 19 people between the ages of 13 and 78. They used three different machine learning algorithms to assess those sequences and identify likely intermediate, forming neural cells. The scientists validated their machine learning outputs by applying the same tools to datasets from mice and adult human cortex cells, and reported a false positive rate of just 0.37 percent.

From all of their analyses, they identified 354 of cells out of hundreds of thousands across their 19 samples that appeared to be precursors to new neurons, including dozens of stem cells and neuroblasts from adults. The cells weren’t distributed uniformly, only showing up in half the adolescent samples and five of the 14 adult samples. However, whether or not the cells were present didn’t seem to wholly correlate with age or documented disease. One of the adults with the highest number of neurogenesis-related cells present was a 58-year-old with no known pathology, per the study.

“We nailed down active neurogenesis in the adult human brain,” Marta Paterlini, a neuroscientist at Karolinska Institutet, tells Popular Science. She co-led the new work over eight years alongside her colleague Ionut Dumitru, who focused on the machine learning side. “We are confident in our data,” Paterlini says. “We would like to put an end to the controversy.”

Still, not everyone in the field agrees that the cells identified in this study are indisputably emerging adult neurons. “When I first heard about this study, I was excited. It’s the sort of approach you would want to use to ID rare subtypes,” Shawn Sorrells, a neuroscientist at the University of Pittsburgh who co-authored the 2018 study with Paredes, tells Popular Science. 

But, after a closer look, he was “disappointed by how few cells they found,” and in his view, there’s an alternate potential explanation. 

“The most likely conclusion is that the cells they are looking for are rare or nonexistent in most people. The other possibility is that the cells they claim are adult neural stem cells are associated with a disease process in these individuals or some other cell type altogether.” 

The human brain is full of cells that do divide and replicate throughout life called glial cells. These are the supportive and connective cells that enable neurons to do the job of conveying nerve signals. Glial cells are neurons’ pit crew. It’s possible that, in their efforts to identify neurons in progress, the study authors may have inadvertently included some glial stem cells in their analysis, Sorrells suggests. 

[ Related: New human brain atlas is the most detailed one we’ve seen yet. ]

Why neuroscientists want answers

Both Sorrells and Paredes believe more research is needed to confirm the new study’s conclusions. Direct, morphological comparisons between human and animal cells could boost the findings, says Paredes. Sorrells suggests we’ll need more advanced brain imaging techniques to really resolve the issue.

“Following the same cells over time to see how they develop. That will be the best evidence for neurogenesis,” he explains, though notes that’s currently not possible.

And so, the science presses on. If, as the new research indicates, some healthy humans do continue to make neurons inside their hippocampuses for life, it could have major implications for psychiatric and neurodegenerative diseases like Alzheimers, where animal studies indicate a dearth of new cells plays a role. It could also aid in our ability to understand and maximize healthy aging and neuroplasticity, Frisén says. 

Perhaps down the line, adult neural stem cells could be used to help people recover after brain trauma, Paterlini suggests. “The lab is working on regenerative medicine, so we will keep going on this.” And maybe all their effort will manage to change minds about how much human minds can change. 

 

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