The role of glia in neurological disease

Glial cells play a very important role in the health of the nervous system and neurons.

Since the belief that glial cells exist only to provide structural support for neurons, it has been increasingly discovered that these microscopic elements are very important for the health of the nervous system and neurons.Since the belief that glial cells exist only to provide structural support for neurons, it has been increasingly discovered that these microscopic elements are very much involved in the proper functioning of the nervous system. Among the usual functions carried out by glia are defense against damage and invaders, nutrition of neurons or enhancement of the electrical impulse, which means that they are much more than a simple support in the development of neurons as was thought in the past.

Since the growing study of glia, we are also looking to see how these cells (which represent the majority of the brain's components) are involved in diseases and disorders. are involved in neurologically rooted diseases and disorders.This has so far only been done in research on the different types of neurons.

It is important to understand to what extent neuroglia are involved in these processes, as this may be one of the ways to find cures in the future.

Quick review: what is glia?

In the Central Nervous System (CNS) we find three main classes of glial cellsoligodendrocytes, responsible for attaching the myelin sheath to neurons; microglia, whose function is to protect the brain; and astrocytes, which have a multitude of functions to assist neurons.

Unlike the CNS, in the peripheral nervous system (PNS) only one main type of neuroglia is found, the Schwanncells, which are further subdivided into three. They are mainly responsible for generating the myelin sheath in the axons of neurons.

• To learn more about this topic, you can consult this article: "Glial cells: much more than the glue of neurons".

Diseases and disorders associated with glia

Today, there is growing evidence that neuroglia there is growing evidence that neuroglia play a role in diseases affecting the CNS, both for better and for worse.both for better and for worse. Here I present a short list of them, covering different types of diseases, where I comment on the involvement (nowadays known) of glial cells in them. It is likely that many more details will be discovered in the future.

1. Temporary and permanent paralysis

A paralysis is suffered when the connection between a number of neurons is lost, because their "communication pathway" has been interrupted.because their "communication pathway" has been broken. In principle, the glia can release substances known as neurotrophics that promote neuronal growth. As occurs in the PNS, this allows mobility to be restored over time. But it is not so in the CNS, suffering a permanent paralysis.

To demonstrate that glia are involved in the non-recovery, since this is the only difference between this neurological alteration when it occurs in the PNS or in the CNS, Albert J. Aguayo conducted an experiment in the 1980s in which rats with damaged spinal cord (i.e., with paralysis) received a transplant of sciatic nerve tissue. rats with damaged spinal cord (i.e., paralysis) received a transplant of sciatic nerve tissue to the affected area. to the affected area. The result was that within two months the rats were able to move naturally again.

In subsequent research, it has been found that there are a number of factors that do not allow the connection to recover completely. One of them is the myelin produced by the oligodendrocytes oligodendrocytes, which, by forming the sheath, prevents the neuron from growing.. The objective of this process is unknown at the moment. Another factor is the excess damage generated by the microglia, since the substances it releases to defend the system are also harmful to the neurons.

2. Creutzfeldt-Jakob disease

This neurodegenerative disease is caused by the infection of a prion, which is an abnormal protein that has gained autonomy. Another name it receives is spongiform encephalopathy, since the brain of those affected ends up full of holes, giving the sensation of a sponge.giving the sensation of a sponge. One of its variants caused a health alert in the 1990s, known as mad cow disease.

Transmitted if ingested, the prion has the ability to cross the selective blood-brain barrier and lodge in the brain. In the CNS, it infects neurons as well as astrocytes and microglia, replicating and killing cells and creating more and more prions.

I have not forgotten about the oligodendrocytes, and it appears that this type of glia resists infection by prions, but does not withstand the oxidative damages that occur as part of the fight by microglia in an attempt to defend the neurons. In 2005, it was reported that the normal state protein that generates the prion is found in the myelin of the CNS, although its function in the CNS is unknown.

3. Amyotrophic Lateral Sclerosis (ALS)

ALS is a degenerative disease that affects motor neurons, which gradually lose their function.The cause is a mutation in the motor neurons, which gradually lose function, causing loss of mobility and even paralysis.

The cause is a mutation in the gene encoding the enzyme Superoxide Dismutase 1 (SOD1), which carries a fundamental function for the survival of cells, which is the elimination of oxygen free radicals. The danger of radicals is that they unbalance the charge in the cytoplasm, leading ultimately to cellular malfunctions and death.

In an experiment with mice with a mutated variant of the SOD1 gene, it was seen how they develop the disease ALS. If the mutation in the motor neurons was prevented, the mice remained healthy. The surprise came with the control group, where only the motor neurons showed the mutation. The theory indicates that in these mice the motor neurons would die and generate the disease. But this did not happen, and to everyone's surprise, the mice were apparently healthy. The conclusion is that the cells near the motor neurons (the glia) had some SOD1-associated mechanism that prevents neurodegeneration. that prevents neurodegeneration.

Specifically, the lifelines of the neurons were astrocytes. If healthy motor neurons cultured in plaque were attached to SOD1-deficient astrocytes, they died. The conclusion drawn is that the mutated astrocytes release some kind of substance toxic to motor neurons, explaining why only this type of neurons die in the development of the disease. However, the toxic agent is still a mystery and the subject of research.

4. Chronic pain

Chronic Pain is a disorder in which pain cells are permanently active. the pain cells remain active without any damage causing their stimulation.. Chronic pain develops when there has been a change in the CNS pain circuitry following injury or illness.

Linda Watkins, a pain researcher at the University of Colorado, suspected that microglia may be involved in chronic pain because they are able to release cytokines, a substance that is secreted in an inflammatory response and activates pain.

To see if he was right, he performed a test on rats with chronic pain caused by spinal cord damage. He administered minocycline, which targets microglia, preventing their activation and, as a consequence, they do not release cytokines. The result was immediate, and the rats stopped suffering pain..

The same study group found the mechanism by which microglia recognize when an area is damaged. Damaged neurons release a substance known as fractalkine, which the microglia recognize and defend by secreting cytokines.. The problem with chronic pain is that for some reason, the microglia keep releasing cytokines, constantly stimulating the production of pain sensation, even though there is no longer damage.

5. Alzheimer's

Alzheimer's is a disease that destroys neurons and their communication, generating a loss of memory.. A hallmark of this disease on the anatomy of the brain is the appearance of senile plaques in different regions of the brain. These plaques are an aggregate of a protein called beta-amyloid, which is toxic to neurons.

This toxic accumulation is generated by astrocytes. This type of glia has the capacity to generate the beta-amyloid peptide, since it can process its precursor, the Amyloid Precursor Protein (APP). Why this occurs is still unclear.

Another marker is that around the plaques large numbers of microglia are observed, which, in an attempt to defend the tissue, clump together to fight the accumulation of amyloid to fight against the accumulation of beta-amyloid and releases toxic substances (such as cytokines, chemokines or reactive oxygen), which instead of helping, promote the death of neurons, as it is toxic to them. Moreover, they have no effect on the senile plaque.