Previous research has suggested neurogenesis — the birth of new neurons — was able to take place in the adult human brain, but a new controversial study published in the journal Nature seems to challenge this idea.

a. Toluidine-blue-counterstained semi-thin sections of the human Granule Cell Layer (GCL) from fetal to adult ages. Note that a discrete cellular layer does not form next to the GCL and the small dark cells characteristic of neural precursors are not present.

Scientists have been struggling to settle the matter of human neurogenesis for quite some time. The first study to challenge the old theory that humans did not have the ability to grow new neurons after birth was published in 1998, but scientists had been questioning this entrenched idea since the 60’s when emerging techniques for labeling dividing cells revealed the birth of new neurons in rats. Another neurogenesis study was published in 2013, reinforcing the validity of the results from 1998.

Arturo Alvarez-Buylla, a neuroscientist at the University of California, San Francisco, and his team conducted a study to test the neurogenesis theory using immunohistochemistry — a process that applies various fluorescent antibodies on brain samples. The antibodies signal if young neurons as well as dividing cells are present. Researchers involved in this study were shocked by the findings.

“We went into the hippocampus expecting to see many young neurons,” says senior author Arturo Alvarez-Buylla. “We were surprised when we couldn’t find them.”

In the new study, scientists analyzed brain samples from 59 patients of various ages, ranging from fetal stages to the age of 77. The brain tissue samples came from people who had died or pieces were extracted in an unrelated procedure during brain surgery. Scientists found new neurons forming in prenatal and neonatal samples, but they did not find any sustainable evidence of neurogenesis happening in humans older than 13. The research also indicates the rate of neurogenesis drops 23 times between the ages one and seven.

But some other uninvolved scientists say that the study left much room for error. The way the brain slices were handled, the deceased patients’ psychiatric history, or whether they had brain inflammation could all explain why the researchers failed to confirm earlier findings.

The 1998 study was performed on brains of dead cancer patients who had received injections of a chemical called bromodeoxyuridine while they were still alive. The imaging molecule — which was used as a cancer treatment — became integrated into the DNA of actively dividing cells. Fred Gage, a neuroscientist involved in the 1998 study, says that this new paper does not really measure neurogenesis.

“Neurogenesis is a process, not an event. They just took dead tissue and looked at it at that moment in time,” he adds.

Gage also thinks that the authors used overly restrictive criteria for counting neural progenitor cells, thus lowering the chances of seeing them in adult humans.

But some neuroscientists agree with the findings. “I feel vindicated,” Pasko Rakic, a longtime outspoken skeptic of neurogenesis in human adults, told Scientific American. He believes the lack of new neurons in adult primates and humans helps preserve complex neural circuits. If new neurons would be constantly born throughout adulthood, they could interfere with preexisting precious circuits, causing chaos in the central nervous system.

“This paper not only shows very convincing evidence of a lack of neurogenesis in the adult human hippocampus but also shows that some of the evidence presented by other studies was not conclusive,” he says.

Dividing neural progenitors in the granule cell layer (GCL) are rare at 17 gestational weeks (orthogonal views, inset) but were abundant in the ganglionic eminence at the same age (data not shown). Dividing neural progenitors were absent in the GCL from 22 gestational weeks to 55 years.

Steven Goldman, a neurologist at the University of Rochester Medical Center and the University of Copenhagen, said, “It’s by far the best database that has ever been put together on cell turnover in the adult human hippocampus. The jury is still out about whether there are any new neurons being produced.” He added that if there is neurogenesis, “it’s just not at the levels that have been presumed by many.”

The debate still goes on. No one really seems to know the answer yet, but I think that’s a positive — the controversy will generate a new wave of research on the subject.

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