DO NEURONS REGENERATE? - NEUROPSYCHOLOGY - 2024

Do neurons regenerate? It has always been thought that not. It seems that most of our neurons are born when we are still in our mother's womb, and with the passage of time, they do not reproduce, but they die little by little.

However, this has not been a cause for concern in normal situations. It is common for a generous number of neurons to be lost each day, what begins to be pathological is an excessive loss like that which occurs in dementia.

But the loss of neurons that is considered normal does not affect our cognitive abilities. In fact, neurons continually reorganize their connections, to always strengthen the most useful at all times and discard the useless.

But what if I told you that evidence has been found that neurons regenerate? Do you know that there are certain areas of our brain in which these cells reproduce, even though we are adults?

Regeneration of neurons in the hippocampus

It appears that, in most mammals, neurons regenerate in the hippocampus and the olfactory bulb. The hippocampus is essential for learning, memory and spatial orientation, while the olfactory bulb makes sense of the information that our smell captures.

This makes sense, because the explanation given to our brain producing new neurons is that it needs to maintain a set of cells with specific properties, but these last a limited time. In addition, they are essential because they are specialized to carry out very specific neural processing.

Apparently, numerous studies claim that neurons are born in a portion of the lateral ventricle and then migrate to the olfactory bulb. There they will integrate with existing cells and will participate in olfactory memory and in the conditioning of fear through smell.

They can also migrate to the dentate gyrus of the hippocampus, acquiring an important role in spatial learning and memory of contextual keys.

Humans differ from other mammals in that they do not have regeneration in the olfactory bulb. However, it has been shown that this regeneration does occur in the hippocampus. It seems that this explains why we are not as dependent on smell as other animals, while we have a higher degree of cognitive adaptation.

Before 1998, it was already known that neurogenesis (the birth of new neurons) existed in adult rodents and monkeys. But what about humans?

In that year, Eriksson and his team were the first to show that neuronal regeneration occurs in the human hippocampus. They used postmortem human brain tissue, proving that neurons reproduce throughout life in the dentate gyrus.

Thus, hippocampal cells have an annual turnover rate of 1.75%. However, human neurogenesis in the cerebral cortex only occurs in our early development and is not maintained into adulthood.

Regeneration of neurons in the striatum

Striated nucleus (striatum)

In 2014, a group of scientists from the Karolinska Institute discovered that neurogenesis exists in the brain of adult humans.

These researchers found neuroblasts in the wall of our lateral ventricle. We can say that neuroblasts are primitive cells that have not yet evolved, and that, in the future, they will differentiate into neurons or glial cells.

But that's not all, they also found that these neuroblasts grow and integrate in a nearby area: the striatum. This part of our brain is essential to control our movements, and damage in this place would produce motor alterations such as tremors and tics.

In fact, the same authors discovered that in Huntington's disease, where motor deficits occur, hardly any neurons are regenerated in the striatum. Also, in advanced stages of the disease, regeneration stops completely.

Regeneration in other brain areas

There are authors who have found adult neuronal regeneration in other unconventional areas, such as the neocortex, piriformis cortex, and limbic structures such as the amygdala, hypothalamus, or preoptic area. The latter have an essential role in social behavior.

However, there are researchers who have obtained contradictory results or have used imprecise methods that have been able to alter the results. Therefore, further research is necessary to confirm these findings.

On the other hand, it should be mentioned that it is difficult to study the regeneration of neurons in humans due to the existing ethical limits. For this reason, there are more advances in the animal field.

However, a non-invasive technique called magnetic resonance spectroscopy has been developed that can explore the existence of progenitor cells in the living human brain.

It is hoped that in the future these techniques can be refined to learn more about neurogenesis in adult humans.

Factors that enhance neuronal regeneration in adults

- Enriched environment and physical activity

It seems that a more complex environment increases the opportunity to live experiences, and produces sensory, cognitive, social and motor stimulation.

This particular fact does not appear to increase neurogenesis, but it does increase the survival of hippocampal cells in rodents and their level of specialization.

However, only voluntary physical activity has been shown to increase neurogenesis, in addition to the survival of these cells in adult mice.

If we consider the enriched environment as greater opportunities to learn, it has been confirmed that learning itself is decisive in hippocampal neurogenesis.

- Learning tasks

In a 1999 study by Gould et al, learning was shown to enhance neurogenesis in the hippocampus. They marked the new cells in rats and observed where they were going as they performed various learning tasks.

Thus, they verified that the number of regenerated neurons doubled in the dentate gyrus when the rats carried out learning tasks that involved the hippocampus. While, in the activities in which the hippocampus did not participate, this increase did not occur.

This is confirmed in other studies, such as that of Shors et al. in 2000, or like that of Van Praag et al. (2002), although they add that new cells evolve and become functional mature cells similar to those already existing in the dentate gyrus.

Regarding the learning activities in which the hippocampus is involved, we find: blink conditioning, in preference to food, or learning of spatial navigation.

- Social interactions

In an interesting study by Lieberwirth & Wang (2012) it was found that positive social interactions (such as mating) increase adult neurogenesis in the limbic system, while negative interactions (such as isolation) decrease it.

However, these results must be contrasted with new studies to be confirmed.

- Neurotrophic factors

Or substances that promote nerve growth, would be those such as BDNF (Brain-derived neurotrophic factor), CNTF (ciliary neurotrophic factor), IGF-1 (Insulin-like growth factor type I), or VEGF (Endothelial growth factor vascular).

- Neurotransmitters

There are certain types of neurotransmitters that regulate cell proliferation.

For example, GABA, which is inhibitory, regulates hippocampal neurogenesis. More specifically, it reduces it, but at the same time increases the integration of the new neurons with the old ones.

Another neurotransmitter, glutamate, slows neuronal regeneration. As if a substance with an opposite effect (antagonist) is injected, regeneration is increased again.

On the other hand, serotonin increases neurogenesis in the hippocampus, while its absence reduces it.

- Antidepressants

In a study by Malberg et al. (2000) have shown that prolonged exposure to antidepressants increases cell proliferation in the hippocampus. However, this has only been found in rats.

Factors that inhibit neuronal regeneration in adults

- Stress

Numerous studies show that an increase in stress produces a significant decrease in neuronal regeneration of the hippocampus.

Furthermore, if the stress is chronic, it reduces both neurogenesis and the survival of these cells.

- Steroids

Corticosteroids, such as glucocorticoids, which are released during the stress response, produce a decrease in hippocampal neurogenesis. The opposite occurs if the levels of this substance are reduced.

Something similar happens with gonadal steroids. In fact, in females, neuronal proliferation varies according to the levels of steroids existing in each phase of the hormonal cycle.

If estrogens are administered to females for less than 4 hours, neuronal proliferation increases. However, if the administration continues up to 48 hours, this proliferation is suppressed.

- Social isolation

It appears that social failure, like isolation, decreases neuronal regeneration and survival in animals such as monkeys, mice, rats, and shrews.

- Drugs abuse

A reduction in neurogenesis and cell survival has been shown due to chronic use of alcohol, cocaine, ecstasy, nicotine, and opioids.

References

1. Eriksson, PT, Ekaterina P., Björk-Eriksson, T., Alborn, AM, Nordborg, C., Peterson, DA & Gage, FH (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4, 1313-1317.
2. Ernst, AA, Alkass, KA, Bernard, SA, Salehpour, MA, Perl, SA, Tisdale, JA, &… Uppsala universitet, TO (2014). Neurogenesis in the Striatum of the Adult Human Brain. Cell, 1072.
3. Gould, E., Beylin, A., Tanapat, P., Reeves, A. & Shors, TJ (1999). Learning enhances adult neurogenesis in the hippocampal formation. Nature Neuroscience, 2, 260-265.
4. Lieberwirth, C. & Wang, Z. (2012). The social environment and neurogenesis in the adult mammalian brain. Front Hum. Neurosci., 6, pp. 1-19.
5. Lieberwirth, C., Pan, Y., Liu, Y., Zhang, Z., & Wang, Z. (2016). Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory. Brain Research, 1644: 127-140.
6. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000). Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci., 20, pp. 9104-9110.
7. Shors, TJ, Miesegaes, G., Beylin, A., Zhao, M., Rydel, T., & Gould, E. (2001). Neurogenesis in the adult is involved in the formation of trace memories. Nature, 410 (6826), 372.
8. Van Praag H., Schinder AF, Christie BR, Toni N., Palmer TD, Gage FH (2002). Functional neurogenesis in the adult hippocampus. Nature; 415 (6875): 1030-4.
9. Yuan, T., Li, J., Ding, F., & Arias-Carrion, O. (2014). Evidence of adult neurogenesis in non-human primates and human. Cell And Tissue Research, (1), 17.