12 March 2018

Adult neurogenesis has become childish

New neurons stop appearing in the human brain after 13 years

Kirill Stasevich, "Science and Life"

We are already used to the fact that nerve cells are restored – at least in part. It is believed that there are two areas in the brain where new neurons continue to appear almost all their lives. One zone is located in the wall of the ventricles of the brain, the other is in the hippocampus, one of the main memory centers. 

Generally speaking, the fact that new nerve cells appear not only during the maturation of the fetus in the womb, but also after birth, was said back in the 60s of the last century. However, at that time, this idea did not receive much support, largely because it was simply impossible to notice new neurons in the brain using the methods of that time. And only in the 90s, when such methods appeared, biologists began to realize that adult neurogenesis – that is, the appearance of new neurons in the adult brain – really exists.

At first it was seen only in animals, but then data began to appear that adult neurogenesis also exists in humans, and in humans new neurons appear only in the hippocampus. "Human" data is based on several approaches. Firstly, dividing cells synthesize DNA, respectively, new neurons can be seen if you give them a special label molecule that they will embed into new DNA chains. 

Secondly, the appearance of new neurons was assessed by the accumulation of the carbon isotope 14 C in the same DNA (according to the radiocarbon method, it turned out that about 700 neurons appear in the adult brain every day). Finally, it is known that cells at different stages of development synthesize different protein molecules, and according to the protein portrait, dividing precursor cells of neurons can be distinguished from ready-made nerve cells, and young, newly formed neurons can also be distinguished from old ones – and protein analysis also seemed to indicate in favor of adult neurogenesis in humans.

However, the results of such studies were still somewhat ambiguous and required additional clarifications. Researchers from the University of California at San Francisco decided to clarify the situation as much as possible and compared brain samples taken postmortem from 59 people, including elderly people, young people, teenagers, children, and premature infants.

neurogenesis.jpg

From left to right: young neurons (green) in the hippocampus of a newborn and people aged 13 and 35 years. Figure from the UCSF press release Birth of New Neurons in the Human Hippocampus Ends in Childhood – VM.

In each sample, the number of dividing cells, progenitors of neurons and young neurons was evaluated. The article in Nature says that if you compare even the first year of life with intrauterine development, you can see that there are already quite a few new, immature neurons in the hippocampus of a one-year-old baby, and then their number only continues to decrease. Thirteen years is the last age when new nerve cells can be noticed here; and if immediately after birth they can be counted more than 1600 per one cm 2, then by the age of seven there are only a couple of such cells per one cm 2. So it is better to call neurogenesis not adult, but childish.

Why did other neuroscientists see new neurons in the adult brain? The authors of the work believe that it's all about the features of the protein portrait of neurons at different stages of life. Young nerve cells are identified by two proteins (DCX and PSA-NCAM), but both are present in mature neurons and even in auxiliary glial cells. And only if both proteins are monitored at the same time, it is possible to distinguish immature neurons from mature ones: immature ones have both proteins at once. As for the labeling of new DNA, the researchers believe that false positive results took place here, that is, the new DNA was seen where it actually wasn't.

On the other hand, it is known from experiments with animals that the proteins by which immature neurons are recognized change with age, and if you delay the preparation of a sample, then one of them is destroyed altogether. However, the researchers took quite a lot of samples of both children's brains and adults for analysis, and they identified young neurons not only by the aforementioned proteins, but also by other signs.

In fact, this is not the first work that calls into question the scale of adult neurogenesis. For example, two years ago, Neuropathology and Applied Neurobiology published an article in which adult neurogenesis in humans was limited to only four years of life. It is also known that even in rats, on which neurogenesis is studied most actively, it drops quite a lot by the middle of life.

And there are also experiments with monkeys that say that neurons in the primate brain mature for a very, very long time, and that after its birth, a young neuron becomes an adult years later, if not decades. So those young neurons that can be seen in the adult human brain could actually appear in the first time after birth.

By themselves, nerve cells are quite plastic: they form and destroy interneuronal contacts, reformat nerve chains, regulate the strength of impulses, etc. It is possible that the adult brain does not really need new neurons – it has enough of those that appeared before birth in early childhood.

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