Neural death: what is it and why does it happen?

All neurons in our body have a life cycle. They are trained, live, perform their functions and eventually die and are replaced. In fact, it is something that is constantly happening in different systems of the body.

However, the nervous system is a special case in which, once in adulthood, hardly any new neurons will be produced. And those 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 we will 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 suggests, to the death of nerve cells called neurons. This has a number of profound repercussions, such as the fact that a cell will no longer be able to fulfill its function of transmitting information (with the consequent decrease in brain efficiency or even loss of function depending on the quantity, surface and functions of dead cells).

However, it is not limited to this, and it is that the death of a neuron can have an effect on neighboring cells: it implies the existence of debris which although in general can be eliminated by the system. , they can also stay there and interfere with normal brain function.

The process by which a neuron dies can vary widely depending on its causes, As well as the results of this death. It is generally considered that there are two major types of neuronal death: that caused naturally by the cell itself or apoptosis and that caused by injury or necrosis.

Programmed neuronal death: apoptosis

In general, we tend to think of neuron death as a negative thing, especially since once in adulthood there are hardly any new neurons (although some areas have been discovered where there is neurogenesis). But neuronal death is not always negative, and in fact throughout our development there are even specific times when it is programmed. We are talking about apoptosis.

Apoptosis is itself the programmed death of body cells, Which allows it to grow by getting rid of unnecessary material. It is a cell death which is beneficial (in general) for the organism and which is used to develop us or to fight against possible damages and diseases (diseased or harmful cells are eliminated). This process is characterized in that it requires energy to occur, it cannot be carried out in the absence of ATP (adenosine triphosphate, a substance from which cells obtain energy).

At the cerebral level this occurs especially at the time of neuronal or synaptic pruning, in which a high percentage of neurons that developed during our early years die in order to allow a more efficient organization of the system. They die off those neurons that don’t make strong enough synapses since they’re not used regularly. and those of more frequent use remain. This allows us to mature and increase efficiency in the use of mental resources and available energy. Another time when apoptosis also occurs is during aging, although in this case the consequences lead to the gradual loss of faculties.

In the process of neuronal apoptosis, the cell itself generates biochemical signals (either by positive induction in which receptors in the membrane bind to certain substances, or by negative or mitochondrial induction in which the suppressing ability is lost) . Certain substances which would generate the activity of apoptotic enzymes) which cause them to condense and alter the cytoplasm, the cell membrane, to cause the cell nucleus to collapse and to fragment DNA. Eventually, the microglial cells phagocytose and remove the remnants of dead neurons, so that they don’t interfere with normal brain function.

A special type of apoptosis is called anoikis, In which the cell loses contact with the material of the extracellular matrix, which ends up causing its death by not being able to communicate.

Necrosis: death by injury

But neuronal death doesn’t just happen preprogrammed to improve system efficiency. They can also die from external causes such as injury, infection or poisoning. This type of cell death is known as necrosis.

Neuronal necrosis is neuronal death caused by the influence of external factors, usually of a harmful nature. This neuronal death is most often detrimental to the subject. It does not require the use of energy, being passive neuronal death. The neuron is out of balance with the damage and loses control of its osmosis, breaking down the cell membrane and releasing its contents. It is common for these leftovers to produce an inflammatory reaction that can lead to various symptoms. In contrast, in apoptosis, the microglia may not properly phagocytize dead cells, leaving remnants that can interfere with the functioning of regulation. And although over time they get phagocytosed, even if removed, they tend to leave a scar of fibrous tissue that interferes with the neural circuit.

It is important to note that necrosis can also occur if, in a process of apoptosis, loss of ATP occurs. Since the system needs energy to produce apoptosis, if left without it, neuronal death cannot occur preprogrammed, so even if the neuron in question dies, the process does not. cannot be completed, causing the death in question to be necrotic.

Neuronal necrosis can occur for several causes. It is common to appear before processes such as hypoxia or anoxia, Stroke, traumatic brain injury or infections. Neuronal death by excitotoxicity is also well known, in which neurons die due to the excessive influence of glutamate (the main excitatory of brain activity), as in the case of certain drug overdoses or poisonings.

The influence of neuronal death on dementias and neurological disorders

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

As we age, our neurons do so with us, dying throughout our lives. Microglia are responsible for protecting the nervous system and phagocytosing the remains of dead neurons (Through apoptotic processes), so that faculties are still lost, the brain generally 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, the microglia do not perform its function of phagocytizing dead cells, leaving debris that causes inflammation of surrounding tissue. . This means that even if too much of the brain is lost, there is still remnants and scar tissue which, as it accumulates, increasingly impairs the performance of the rest of the brain, in turn facilitating greater death. neuronal.

Although these are recent experiments that need to be replicated to get more data and falsify the results, this data may allow us to better understand the process by which the nervous system deteriorates, so that we can establish better strategies and treatments that mitigate neuronal destruction and possibly, in the long term, to stop previously incurable diseases.

Bibliographical references:

  • Consentino, C. (1997). Apoptosis and the nervous system. Annals of the Faculty of Medicine, 58 (2). Enlarged National University of San Marcos.
  • Becerra, LV; Pebre, HJ (2009). Neuronal apoptosis: the diversity of signals and cell types. Medical Colombia 40 (1): 125-133, University of La Vall. Faculty of Health. Colombia.
  • Abiega, O. et al. (2016). Neuronal hyperactivity disrupts ATP microgradients, affects microglial motility and reduces expression of phagocytic receptors which triggers apoptosis / decoupling of microglial phagocytosis. PLoS biology.

Leave a Comment