Do neurons regenerate?

Science sheds light on whether neuronal regeneration really exists.

Do neurons regenerate? The answer to this question is not simple, and for years scientific studies have been affirming that neurogenesis or neuronal regeneration occurs from birth and throughout our lives.

However, the most recent research points in the opposite direction and suggests that neurogenesis does not occur in adult brains, or not in the way it was thought to occur.

In this article we explain what neurogenesis consists of, and we give you the keys to understand the current controversy about whether or not neurons regenerate in adulthood.

• Recommended article: "Types of neurons: characteristics and functions".

Neurogenesis: what does it consist of?

Neurogenesis refers to the process by which new neurons are generated in the brain.. This phenomenon is crucial during embryonic development, but apparently also continues in certain brain regions after birth and for the rest of our lives.

The mature brain has a multitude of specialized areas and neurons that differ in their structure and connections. The hippocampus, for example, which is an area of the brain that plays an important role in memory and spatial navigation, has at least 27 different types of neurons.

This incredible neuronal diversity in the brain is a product of neurogenesis during embryonic development. During pregnancy, and thanks to stem cells, cell differentiation occurs, a process by which these neurons undergo genetic modifications and acquire the morphology and functions of a specific cell type, at certain times and in certain brain regions.

Stem cells can divide indefinitely to generate more stem cells or to differentiate into more specialized cells, such as progenitor cells. These can differentiate into various specific types of neurons (neurogenesis); or they can differentiate into glial progenitor cells, which give rise to glial cells such as astrocytes, oligodendrocytes and microglia (gliogenesis).

Do neurons regenerate?

Neuroplasticity refers to the adaptive capacity of the nervous system to change throughout life based on learning acquired through behavior and experiences. The brain can create new connections or strengthen existing ones between neurons and different neural circuits. This process of improving communication between neurons is called synaptic plasticity.

On the other hand, the brain is also capable, at least in some areas, of producing progenitor cells that produce neurogenesis. Until relatively recently, neuroscientists believed that adult neurogenesis did not occur; that is, it was assumed that the birth of neurons was limited to the period of time comprising embryonic development and early childhood, and that, after this period of rapid growth, the nervous system was incapable of regenerating itself.

This belief arose from the fact that, unlike most cells in our body, mature neurons do not undergo cell division, a process by which one cell (the mother cell) divides into two or more new cells (the daughter cells). This dogma was challenged starting a couple of decades ago, when evidence that neurons regenerate in the adult human brain was first reported.

Since then, numerous studies have determined that new neurons are born throughout life in specific neurogenic areas of the brain, numerous studies have determined that new neurons are born throughout life in specific neurogenic areas of the brainThe subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone (the ejido located under the lateral ventricles), and not from the division of mature cells, but from the differentiation of neural stem cells.

Neural stem cells

Stem cells are undifferentiated Biological cells that can generate different types of specialized cells through cell differentiation. Some can become any type of differentiated cell in our body: these are called totipotent stem cells; and others can become almost any cell: pluripotent stem cells.

Other types of stem cells already have some degree of specialization, and can only transform into specific, closely related cells (multipotent stem cells), such as the different cell types of a tissue.

There are also stem cells that are already committed to being a specific type of cell (unipotent stem cells), but retain the ability to develop into specific, closely related cells (multipotent stem cells).but which retain the capacity for self-renewal through cell division. This capacity for self-renewal is another distinguishing feature of stem cells.

In summary, neural stem cells are multipotent stem cells of the nervous system that are self-renewing, and are capable of generating both new neurons and glial cells (non-neuronal brain cells that serve as support and protection for neurons).

Neurogenesis in the adult brain: the controversy

Most research on adult neurogenesis has focused on one brain region: the dentate gyrus of the hippocampus. Neurogenesis has been observed in this brain area in all mammalian species studied to date.

In the adult human brain, this process of neuronal regeneration appears to occur in the hippocampus, a region particularly important for learning.a region particularly important for learning and memory, emotions, mood, anxiety or stress response.

Another area where evidence of adult neurogenesis has been found in humans is the striatum, a brain region known for its role in motor coordination, but also in other processes such as the regulation of reward, aversion, motivation or pleasure.

The striatum has been identified as a key structure in higher cognitive functions, particularly in cognitive flexibility, the ability to adapt behavioral goals in response to changing environmental demands.

Nevertheless, the controversy is ongoing, as recent research has shown that the formation of new neurons in hippocampal structures declines in childhood and is very rare or nonexistent in adult brains.

The study, published in 2018 in the journal Nature, concluded that recruitment of young neurons in the hippocampus declines rapidly during the first years of life, and that neurogenesis in the dentate gyrus of this brain structure does not persist or is extremely rare in adult humans.

The explanation for the latter may lie in the fact that, although markers have been found to be frequently associated with new neurons, such markers can also be found in neurons that have been born during development and have remained in the cells for years..

However, the opposite explanation has also been put on the table by neuroscientists in favor of adult neurogenesis, and it has been argued that the fact that no new neurons are observed does not mean that they are not there, but simply that we are not able to detect them.

Furthermore, this study also suggests that plasticity in the adult hippocampus does not require the continuous generation of new neurons; according to the authors, it is possible that the brain has a "reservoir" of neurons that never fully mature, or that mature slowly and can make changes, so that it is not necessary to integrate new neurons. This hypothesis has yet to be tested.

Be that as it may, there is currently no clear consensus in the scientific community as to whether or not neurons regenerate in adult brains.. The evidence is contradictory and the most recent research seems to call into question decades of research on adult neurogenesis.

So the only certainty we have at the moment is that much research remains to be done.

Bibliographic references:

• Kempermann, G. (2016). Adult neurogenesis: an evolutionary perspective. Cold Spring Harbor perspectives in biology, 8(2).

• Kozorovitskiy, Y., & Gould, E. (2008). Adult neurogenesis in the hippocampus. Handbook of developmental cognitive neuroscience, 51-62.

• Song, J., Zhong, C., Bonaguidi, M. A., Sun, G. J., Hsu, D., Gu, Y., ... & Deisseroth, K. (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature, 489(7414), 150.

• Sorrells, S. F., Paredes, M. F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K. W., ... & Chang, E. F. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature, 555(7696), 377.