Nerve cells are being restored

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

The popular expression "Nerve cells do not recover" is perceived by everyone from childhood as an immutable truth. However, this axiom is nothing more than a myth, and new scientific data refutes it.

Nature lays in the developing brain a very high margin of safety: during embryogenesis, a large excess of neurons is formed. Almost 70% of them die before the birth of a child. The human brain continues to lose neurons after birth, throughout life. This cell death is genetically programmed. Of course, not only neurons die, but also other cells of the body. Only all other tissues have a high regenerative capacity, that is, their cells divide, replacing the dead.

The regeneration process is most active in the cells of the epithelium and hematopoietic organs (red bone marrow). But there are cells in which the genes responsible for reproduction by division are blocked. In addition to neurons, these cells include the cells of the heart muscle. How do people manage to preserve intelligence until very old age, if nerve cells die and are not renewed?

One of the possible explanations: not all neurons "work" simultaneously in the nervous system, but only 10% of neurons. This fact is often cited in popular and even scientific literature. I have repeatedly had to discuss this statement with my domestic and foreign colleagues. And none of them understands where this figure came from. Any cell lives and "works" at the same time. In each neuron, metabolic processes take place all the time, proteins are synthesized, nerve impulses are generated and transmitted. Therefore, leaving the hypothesis of "resting" neurons, let us turn to one of the properties of the nervous system, namely, to its exceptional plasticity.

The meaning of plasticity is that the functions of dead nerve cells are taken over by their surviving "colleagues", who increase in size and form new connections, compensating for the lost functions. The high, but not infinite efficiency of such compensation can be illustrated by the example of Parkinson's disease, in which there is a gradual death of neurons. It turns out that until about 90% of the neurons in the brain die, the clinical symptoms of the disease (trembling of the limbs, limitation of mobility, unsteady gait, dementia) do not appear, that is, the person looks practically healthy. This means that one living nerve cell can replace nine dead.

But the plasticity of the nervous system is not the only mechanism that allows the preservation of intelligence to a ripe old age. Nature also has a fallback - the emergence of new nerve cells in the brain of adult mammals, or neurogenesis.

The first report on neurogenesis appeared in 1962 in the prestigious scientific journal Science. The article was titled "Are New Neurons Forming in the Brain of Adult Mammals?" Its author, Professor Joseph Altman from Purdue University (USA), with the help of an electric current, destroyed one of the structures of the rat's brain (the lateral geniculate body) and injected there a radioactive substance that penetrates the newly emerging cells. A few months later, the scientist discovered new radioactive neurons in the thalamus (part of the forebrain) and cerebral cortex. Over the next seven years, Altman published several more studies proving the existence of neurogenesis in the brain of adult mammals. However, then, in the 1960s, his work caused only skepticism among neuroscientists, their development did not follow.

And only twenty years later neurogenesis was "rediscovered", but already in the brain of birds. Many songbird researchers have noticed that during each mating season, the male canary Serinus canaria sings a song with new "knees". Moreover, he does not adopt new trills from his fellows, since the songs were updated even in isolation. Scientists began to study in detail the main vocal center of birds, located in a special section of the brain, and found that at the end of the mating season (in canaries it occurs in August and January), a significant part of the neurons of the vocal center died, probably due to excessive functional load … In the mid-1980s, Professor Fernando Notteboom from Rockefeller University (USA) was able to show that in adult male canaries, the process of neurogenesis occurs in the vocal center all the time, but the number of formed neurons is subject to seasonal fluctuations. The peak of neurogenesis in canaries occurs in October and March, that is, two months after mating seasons. That is why the "music library" of the male canary's songs is regularly updated.

In the late 1980s, neurogenesis was also discovered in adult amphibians in the laboratory of the Leningrad scientist Professor A. L. Polenov.

Where do new neurons come from if nerve cells are not dividing? The source of new neurons in both birds and amphibians turned out to be neuronal stem cells from the wall of the ventricles of the brain. During the development of the embryo, it is from these cells that the cells of the nervous system are formed: neurons and glial cells. But not all stem cells turn into cells of the nervous system - some of them "hide" and wait in the wings.

It has been shown that new neurons arise from stem cells of the adult organism and in lower vertebrates. However, it took almost fifteen years to prove that a similar process occurs in the mammalian nervous system.

Advances in neuroscience in the early 1990s led to the discovery of "newborn" neurons in the brains of adult rats and mice. They were found mostly in the evolutionarily ancient parts of the brain: the olfactory bulbs and the hippocampal cortex, which are mainly responsible for emotional behavior, stress response, and regulation of mammalian sexual functions.

Just like in birds and lower vertebrates, in mammals, neuronal stem cells are located near the lateral ventricles of the brain. Their transformation into neurons is very intensive. In adult rats, about 250,000 neurons are formed from stem cells per month, replacing 3% of all neurons in the hippocampus. The lifespan of such neurons is very high - up to 112 days. Neuronal stem cells travel a long way (about 2 cm). They are also able to migrate to the olfactory bulb, turning into neurons there.

The olfactory bulbs of the mammalian brain are responsible for the perception and primary processing of various odors, including the recognition of pheromones - substances that in their chemical composition are close to sex hormones. Sexual behavior in rodents is primarily regulated by the production of pheromones. The hippocampus is located under the cerebral hemispheres. The functions of this complex structure are associated with the formation of short-term memory, the realization of certain emotions and participation in the formation of sexual behavior. The presence of constant neurogenesis in the olfactory bulb and hippocampus in rats is explained by the fact that in rodents these structures bear the main functional load. Therefore, the nerve cells in them often die, which means that they need to be renewed.

In order to understand what conditions influence neurogenesis in the hippocampus and olfactory bulb, Professor Gage from Salk University (USA) built a miniature city. The mice played there, did physical education, looked for exits from the labyrinths. It turned out that in "urban" mice, new neurons arose in a much larger number than in their passive relatives, mired in a routine life in a vivarium.

Stem cells can be removed from the brain and transplanted into another part of the nervous system, where they become neurons. Professor Gage and his colleagues conducted several similar experiments, the most impressive of which was the following. A section of brain tissue containing stem cells was transplanted into the destroyed retina of a rat eye. (The light-sensitive inner wall of the eye has a "nervous" origin: it consists of modified neurons - rods and cones. When the light-sensitive layer is destroyed, blindness sets in.) The transplanted brain stem cells turned into retinal neurons, their processes reached the optic nerve, and the rat regained its sight! Moreover, when transplanting brain stem cells into an intact eye, no transformations took place with them. Probably, when the retina is damaged, some substances are produced (for example, the so-called growth factors) that stimulate neurogenesis. However, the exact mechanism of this phenomenon is still not clear.

Scientists were faced with the task of showing that neurogenesis occurs not only in rodents, but also in humans. To this end, researchers under the guidance of Professor Gage recently performed sensational work. In one of the American oncological clinics, a group of patients with incurable malignant neoplasms took the chemotherapeutic drug bromodioxyuridine. This substance has an important property - the ability to accumulate in the dividing cells of various organs and tissues. Bromodioxyuridine is incorporated into the DNA of the mother cell and is stored in daughter cells after the mother's cells divide. Pathological research has shown that neurons containing bromodioxyuridine are found in almost all parts of the brain, including the cerebral cortex. So these neurons were new cells that emerged from stem cell division. The find unconditionally confirmed that the process of neurogenesis also occurs in adults. But if in rodents neurogenesis occurs only in the hippocampus, then in humans it can probably invade more extensive areas of the brain, including the cerebral cortex. Recent studies have shown that new neurons in the adult brain can be formed not only from neuronal stem cells, but from blood stem cells. The discovery of this phenomenon has caused euphoria in the scientific world. However, the publication in the journal "Nature" in October 2003 cooled enthusiastic minds in many ways. It turned out that blood stem cells do indeed penetrate the brain, but they do not turn into neurons, but merge with them, forming binuclear cells. Then the "old" nucleus of the neuron is destroyed, and it is replaced by the "new" nucleus of the blood stem cell. In the rat's body, blood stem cells mainly merge with the giant cells of the cerebellum - Purkinje cells, although this happens quite rarely: only a few merged cells can be found in the entire cerebellum. More intense fusion of neurons occurs in the liver and heart muscle. It is not yet clear what the physiological meaning is in this. One of the hypotheses is that blood stem cells carry with them new genetic material, which, entering the "old" cerebellar cell, prolongs its life.

So, new neurons can arise from stem cells even in the adult brain. This phenomenon is already widely used to treat various neurodegenerative diseases (diseases accompanied by the death of neurons in the brain). Stem cell preparations for transplantation are obtained in two ways. The first is the use of neuronal stem cells, which in both the embryo and the adult are located around the ventricles of the brain. The second approach is the use of embryonic stem cells. These cells are located in the inner cell mass at an early stage of embryo formation. They are able to transform into almost any cell in the body. The biggest challenge in working with embryonic cells is getting them to transform into neurons. New technologies make it possible to do this.

Some hospitals in the United States have already formed "libraries" of neuronal stem cells obtained from embryonic tissue, and are being transplanted into patients. The first attempts at transplantation are yielding positive results, although today doctors cannot solve the main problem of such transplants: the rampant multiplication of stem cells in 30-40% of cases leads to the formation of malignant tumors. No approach has yet been found to prevent this side effect. But despite this, stem cell transplantation will undoubtedly be one of the main approaches in the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's, which have become the scourge of developed countries.