NEUROGENESIS: CHARACTERISTICS AND REGULATION - NEUROPSYCHOLOGY - 2025

The Neurogenesis is the birth of new neurons from stem cells and progenitor cells. It occurs during embryonic development when the nervous system is formed. Recent evidence has shown that neurogenesis continues in adult primates and humans.

Neurons are the functional components of the nervous system and are responsible for the processing and transmission of information. Contrary to what was long thought, the adult nervous system can generate new neurons, that is, it has a certain capacity to regenerate, so that the new production of neurons is not restricted only to embryonic and neonatal life.

All mammals have cells that replicate in many organs and in some cases, especially in the blood, skin, and intestine, stem cells exist throughout life, contributing to rapid cell replacement.

For example, the intestine fully regenerates its cells every 10.7 years. Regeneration of the nervous system, specifically the brain, is much more limited, but that does not mean that it does not exist.

Characteristics of neurogenesis

Neuron

Insects, fish, and amphibians can replicate neural cells throughout life. An exception to this rule of self-repair and continuous growth was thought to be the mammalian brain and spinal cord.

Today we know that this long-accepted limitation is not entirely true, since there are well-differentiated areas of the brain that can generate new neurons throughout life.

Thus, there are neural stem cells throughout life in the adult brain that can renew and give rise to new neurons, astrocytes and oligodendrocytes, just as in the developing brain.

In these areas of the adult mammalian brain (dentate gyrus and subventricular area) there are cells with mitotic activity, which can be classified into two groups:

Stem or stem cells

They are those capable of dividing indefinitely and differentiating into different types of specialized cells, with a cell cycle greater than 28 days.

Neural progenitor cells

With a 12-hour cell cycle, they are neural cells with a more limited capacity for self-renewal and expansion, and with the potential to differentiate into a few types of neurons.

Neuronal progenitors and glial progenitors would be the cells committed to differentiate only into neurons or glia, respectively. Neural progenitors determined to a specific neuron type could be the ideal replacement tool to treat the injured central nervous system.

Regulation of neurogenesis in the adult brain

Neurogenesis in the adult brain is positively or negatively regulated by various mechanisms. In addition, there are internal and external factors that participate in such regulation.

Internal factors include the expression of genes, molecules, growth factors, hormones, and neurotransmitters; age is another internal factor involved in neurogenesis. External factors include environmental and pharmacological stimuli.

-Internal factors

Genetic and molecular

Among the genetic factors that induce neurogenesis and embryonic morphogenesis, the expression of genes can be mentioned. These genes also participate in regulating cell proliferation and differentiation in neurogenic areas of the adult brain.

Some of these genes are expressed to varying degrees in the germ regions of the adult brain in response to stimuli or lesions in this area.

Growth factors

The expression of various growth factors, such as Brain Derived Neurotrophic Factor (BDNF) involved in the regulation of cell fate, can determine the size of the neuronal or glial population, both in developing brains and in the adult brain.

These factors are overexpressed in different neurodegenerative models such as Alzheimer's disease or Parkinson's disease, where they participate as protective factors against neuronal damage or as inductive factors during the generation and differentiation of new cells that replace the injured cells.

In this context, intracerebroventricular administration of brain-derived neurotrophic factor (BDNF) has been shown to increase neurogenesis in the olfactory bulb and hippocampus.

Thus, we can conclude that these growth factors stimulate neurogenesis in the adult brain.

Neurotransmitters

It is currently known that various neurotransmitters participate as factors that regulate neurogenesis in the adult brain. Among the most studied are glutamate, serotonin (5-HT), norepinephrine and dopamine.

Glutamate is considered the most important neurotransmitter for brain function. It is known to regulate neurogenesis in the hippocampus of adult animals.

The participation of 5-HT in neurogenesis has been demonstrated in several studies, so that the inhibition of its synthesis has allowed us to see a decrease in the proliferation rate both in the hippocampus and in the subventricular zone (ZSV) of rats.

The noradrenergic system is another implicated in neurogenesis in the adult brain. By inhibiting norepinephrine release, cell proliferation in the hippocampus has been shown to decrease.

Lastly, dopamine is another important neurotransmitter involved in the regulation of neurogenesis both in the subventricular zone and in the hippocampus of the adult brain. It has been experimentally shown that the decrease in dopamine decreases the generation of new neurons, both in the subventricular area and in the dentate gyrus of the hippocampus.

Hormones

Some studies indicate that ovarian steroids, as well as endogenous estrogens, have a stimulating effect on cell proliferation. However, adrenal steroids such as corticosteroids suppress cell proliferation in areas such as the dentate gyrus of the hippocampus.

A study in rats shows that the rate of neurogenesis increases 65% during pregnancy and reaches its peak just before delivery, which coincides with prolactin levels.

Age

Age is known to be one of the most important internal factors in the regulation of neurogenesis in the brain.

Neurogenesis in the developing brain is very high, but as we reach adulthood and age, it decreases drastically, although not disappearing altogether.

-External factors

Environmental

Neurogenesis is not a static biological process, since its rate is variable and depends on the environment. Physical activity, enriched environments, energy restriction, and modulation of neuronal activity, among other factors, are known to act as positive regulators of neurogenesis.

Animals living in an enriched environment show an increase in neurogenesis in the dentate gyrus. However, in animals that live under stress conditions or in a poorly enriched environment, neurogenesis in this area is diminished or totally inhibited.

Furthermore, alterations in the hypothalamic-pituitary-adrenal axis, induced by persistent stress situations during development, decrease the generation of new cells in the dentate gyrus. Thus, it is known that cell proliferation in the dentate gyrus decreases due to the effect of glucocorticoids, which are released in response to stress.

Thus, it has been observed how voluntary exercise and environmental enrichment improve the performance of young and old mice in the Morris water maze (a task to test hippocampal-dependent learning and memory).

It has also been observed that neurogenesis can be modulated by the social status of animals and is likely to be mediated by molecules such as the brain-derived neurotrophic factor mentioned above.

Lastly, experiences that are associated with improved cognition presumably do so by stimulating the neural network of the hippocampus.

In fact, hippocampal-dependent learning is one of the main regulators of neurogenesis (study). The hippocampus is responsible for the formation of new memories, declarative memory and episodic and spatial memory. Therefore, the proliferation of new neurons in this area of ​​the brain is very important.

How to enhance neurogenesis?

Having explained what neurogenesis is and by what factors it is regulated, you might wonder if something can be done to prevent the decrease in neurogenesis characteristic of aging and stimulate the creation of new neurons. It is your lucky day because the answer is yes. Here are some tips to get it done.

Exercise

The decrease in neurogenesis typical of aging can be prevented or reversed by physical exercise. In fact, older adults who exercise throughout their lives have less loss of brain tissue than sedentary individuals.

On the other hand, physically fit older people perform better on cognitive tests than their sedentary peers (study).

Enriched environments

Adult neurogenesis is dynamically regulated by many physiological stimuli.

Reading, learning new skills, meeting new people, games and tasks that require thinking, having hobbies, traveling or experiences such as having children, among many others, are activities that represent a challenge for our cognition with the consequent brain plasticity and new production of neurons.

Avoid chronic stress

Stress is an acute and adaptive response to the environment that helps us on many occasions to solve problems and escape possible dangers.

However, our way of living full of work and worries means that we are with a constant and chronic level of stress, which, far from being adaptive, can cause us serious physical and psychological problems.

This chronic stress and its consequent high levels of adrenal hormones such as cortisol, has been shown to cause neuronal death and suppression of neurogenesis (study).

Therefore, avoiding stress with alternatives such as yoga, relaxation, good rest, and sleep hygiene would avoid this dreaded neuronal death caused by chronic stress.

Eat well

Food is no less important. Calorie restriction, intermittent fasting, and a diet high in polyphenols and polyunsaturated fatty acids have been shown to benefit cognition, mood, aging, and Alzheimer's disease.

With special attention to improving structural and functional plasticity in the hippocampus, increasing the expression of neurotrophic factors, synaptic function and adult neurogenesis (study).

This does not mean that you do not eat or that you go on a diet, but that it is not good to eat until you puff up or eat processed food. Eat healthy and in moderation.

Polyphenols are found in foods such as grape seeds, apple, cocoa, fruits such as apricots, cherries, blueberries, pomegranates, etc., and in beverages such as red wine. They are also present in nuts, cinnamon, green tea, and chocolate (dark chocolate not milk chocolate).

Polyunsaturated fatty acids are present in fatty fish (blue fish), in fish oils and in shellfish, as well as in seed oils and in green leafy vegetables.

References

1. Gage, FH (2002). Neurogenesis in the Adult Brain. The Journal of Neuroscience, 22 (3), 612-613.
2. Arias-Carrión, O., Olivares-Bañuelos, T. & Drucker-Colin, R. (2007). Neurogenesis in the adult brain. Journal of Neurology, 44 (9), 541-550.
3. Zhao, C., Deng, W. & Gage, FH (2008). Mechanisms and Functional Implications of Adult Neurogenesis. Cell, 132 (4), 645-660.
4. Ming, GL & Song, H. (2011). Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron, 70 (4), 687-702.
5. Murphy, T., Pereira Dias, G. & Thuret, S. (2014). Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap. Neural Plasticity, 2014, 1-32.