Neuronal death: what is it and why does it occur?

Neurons, at some point, stop functioning. What is the cause of this?

All neurons in our body have a life cycle. They are formed, they live, they perform their functions and finally they die and are replaced. In fact, this is something that happens constantly in different systems of the organism.

However, the nervous system is a particular case in which, once in adulthood, hardly any new neurons will be produced. And the ones we already have will not live forever: little by little and for different reasons, they will degenerate and die. That is why, in this article in this article we are going to talk about neuronal death and the two main processes by which it occurs..

What is neuronal death?

The concept of neuronal death refers, as the name itself indicates, to the death of nerve cells known as neurons. This entails a series of far-reaching repercussions, such as the fact that the cell will no longer be able to carry out its function of transmitting information (with the consequent decrease in brain efficiency or even the loss of functions depending on the number, area and functions of the dead cells).

However, it is not limited to this, and the death of a neuron can also have an effect on neighboring cells: it implies the existence of some remains that, although they can generally be eliminated by the system, they can also remain in it and interfere with the normal functioning of the brain.

The process by which a neuron dies can vary greatly depending on its causes, as can the results of such death.The process by which a neuron dies can vary greatly depending on its causes, as can the results of such death. It is generally considered that there are two main types of neuronal death: that produced naturally by the cell itself or apoptosis and that produced by injury or necrosis.

Programmed neuronal death: apoptosis

In general, we tend to consider the death of neurons as something negative, especially considering that once in adulthood practically no new neurons are produced (although some areas have been discovered in which neurogenesis does occur). But neuronal death is not always negative, and in fact throughout our development there are even specific moments in which it is programmed. We are talking about apoptosis.

Apoptosis is in itself the programmed death of the organism's cells, which allows it to develop.which allows it to develop by getting rid of unnecessary material. It is a cell death that is beneficial (generally) for the organism and serves to develop or to fight against possible damage and diseases (diseased or harmful cells are eliminated). This process is characterized by the fact that it requires energy to occur and cannot take place in the absence of ATP (adenosine triphosphate, a substance from which the cells obtain energy).

At the cerebral level this occurs especially at the moment of neuronal or synaptic pruning, when a high percentage of the neurons that have been developing during our early years die in order to allow a more efficient organization of the system. Those neurons that do not establish sufficiently strong synapses because they are not used regularly die, and those of more frequent use remain. and those of more frequent use remain. This allows our maturation and the increase of efficiency in the use of mental resources and available energy. Another moment in which apoptosis also occurs is during aging, although in this case the consequences generate the progressive loss of faculties.

In the process of neuronal apoptosis, the cell itself generates biochemical signals (either by positive induction in which the membrane receptors bind to certain substances or by negative or mitochondrial induction in which the capacity to suppress certain substances that would generate the activity of apoptotic enzymes is lost) that cause the cytoplasm and cell membrane to condense and alter, the cell nucleus to collapse and the DNA to fragment. Finally, the microglial cells eventually phagocytize and eliminate the remains of the dead neurons, so that they do not interfere with the normative functioning of the brain.

A special type of apoptosis is the so-called anoikisisin which the cell loses contact with the material of the extracellular matrix, which ultimately leads to its death because it is unable to communicate.

Necrosis: death due to injury

But neuronal death does not only occur in a preprogrammed manner as a way of improving the efficiency of the system. They can also die due to external causes such as injury, infection or intoxication.. This type of cell death is known as necrosis.

Neuronal necrosis is neuronal death caused by the influence of external factors, generally of an injurious nature. This neuronal death is mostly detrimental to the subject. It does not require the use of energy, being a passive neuronal death. The neuron is unbalanced by the damage and loses control of its osmosis, breaking the cell membrane and releasing its contents. It is common for these remains to produce an inflammatory reaction that can generate various symptoms. Contrary to what happens in apoptosis, it is possible that the microglia do not manage to phagocytose the dead cells correctly, leaving remnants that can interfere with normal functioning. And although they are eventually phagocytosed, even if they are removed they tend to leave a scar of fibrous tissue that interferes with neuronal circuitry.

It is important to note that necrosis can also occur if ATP is lost in the process of apoptosis. Since the system needs energy to produce apoptosis, if it runs out of energy, neuronal death cannot occur in a preprogrammed manner so that although the neuron in question dies, the process cannot be completed, which will result in the death in question being necrotic.

Neuronal necrosis can occur due to multiple causes. It is common in processes such as hypoxia or anoxia, stroke, stroke, trauma, traumatic brain injury, and so on.It is common in processes such as hypoxia or anoxia, cerebrovascular accidents, cranioencephalic trauma or infections. Also well known is neuronal death due to excitotoxicity, in which neurons die due to the excessive influence of glutamate (the main excitatory agent of brain activity), as occurs in the case of some drug overdoses or drug intoxication.

The influence of neuronal death in dementias and neurological disorders

Neuronal death can be observed in a large number of situations, not all of them clinical. However, it is worth highlighting a recently discovered phenomenon in the relationship between dementias and neuronal death.

As we age, our neurons age with us, dying throughout our lives. Microglia are responsible for protecting the nervous system and phagocytizing the remains of dead neurons (through apoptotic processes). (through apoptotic processes), so that even as we lose faculties, the brain usually remains healthy within the limits of normal aging.

However, recent research seems to indicate that in people with dementia, such as Alzheimer's disease, or epilepsy, microglia do not exercise their function of phagocytizing dead cells, leaving remnants that generate inflammation of the surrounding tissues. This means that although brain mass is lost, there are still remnants and scar tissues that, as they accumulate, increasingly impair the performance of the rest of the brain, in turn facilitating greater neuronal death.

Although these are recent experiments that need to be replicated to obtain more data and falsify the results, these data may help us to better understand the process by which the nervous system deteriorates, so that we can establish better strategies and treatments to alleviate neuronal destruction and perhaps, in the long run, to stop incurable diseases that have been incurable until now.

Bibliographical references:

• Consentino, C. (1997). Apoptosis and Nervous System. Annals of the Faculty of Medicine, 58 (2). Universidad Nacional Mayor de San Marcos.
• Becerra, L.V.; Pimienta, H.J. (2009). Neuronal apoptosis: the diversity of signals and cell types. Colombia Médica 40 (1): 125-133. Universidad del Valle. Facultad de Salud. Colombia.
• Abiega, O. y cols. (2016). Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling. PLoS Biology.