The role of glia in neurological disease

Since the belief appeared that glial cells only exist to give structural support to neurons, it is increasingly discovered that these microscopic elements are highly involved in the proper functioning of the nervous system. Among the usual functions of those carried out by glia we find defense against damage and invaders, nutrition of neurons or improvement of the electrical impulse, which means that they are much more than a simple support in the development of neurons as it was thought in the past.

Since the growing study of glia, there is also a search to see how these cells (which represent the majority of the components of the brain) are implicated in neurological root diseases and disorders, something that until now was only done in the investigation of the different types of neurons.

It is important to understand the extent to which neuroglia are involved in these processes, as this may be one of the pathways to finding cures in the future.

Quick review: what is glia?

In the Central Nervous System (CNS) we find

three main classes of glial cells: the oligodendrocytes, responsible for placing the myelin sheath to neurons; microglia, whose function is to protect the brain; and astrocytes, which have a multitude of functions to help neurons.

Unlike the CNS, Only one major type of neuroglia is found in the Peripheral Nervous System (PNS), Sch cells.wann, which are further subdivided into three. Mainly, they are responsible for generating the myelin sheath in the axons of neurons.

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

Glia-associated diseases and disorders

Currently, there is increasing evidence that neuroglia play a role in diseases that affect the CNS, Both as for well and for worse. Here I present a short list of them, covering different types of diseases, where I comment on the involvement (which is known today) of glial cells in them. Many more details are likely to be discovered in the future.

1. Temporary and permanent paralysis

A paralysis is suffered when the connection between a series of neurons is lost, because their "communication path" has been broken. In principle, glia can release substances known as neurotrophs that promote neuronal growth. As in the PNS, this allows mobility to be regained over time. But this is not the case in the CNS, suffering from permanent paralysis.

To demonstrate that glia are involved in non-recovery, since it is the only difference between this neurological alteration when it occurs in the PNS or in the CNS, Albert J. Aguayo, carried out an experiment in the 80s in which rats with spinal cord damage (i.e., paralysis), received a transplant of sciatic nerve tissue towards the affected area. The result is that in two months the rats moved again naturally.

In subsequent investigations, it has been found that there is a sum of factors that does not allow the total recovery of the connection. One of them is the myelin itself that they produce. oligodendrocytes, which, by forming the sheath, prevent neuron growth. The purpose of this process is unknown at this time. Another factor is the excess damage generated by microglia, since the substances it releases to defend the system are also harmful to neurons.

2. Creutzfeldt-Jakob disease

This neurodegenerative disease is caused by infection with 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. One of its variants caused a health alert in the nineties, known as mad cow disease.

Transmitted if ingested, the prion has the ability to pass through the selective blood brain barrier and stay 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 the oligodendrocytes, and it seems that this type of glia resists infection by prions, but does not support oxidative damage that appear as part of the fight carried out by microglia in an attempt to defend neurons. In 2005, it was reported that the normal protein that generates the prion is found in the myelin of the CNS, although its function in it was unknown.

3. Amyotrophic Lateral Sclerosis (ALS)

ALS is a degenerative disease that affects motor neurons., which little by little lose functionality, causing loss of mobility until reaching 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 free radicals from the oxygen. The danger of radicals is that they unbalance the charge in the cytoplasm, ultimately leading to cell malfunction and death.

In an experiment with mice with a mutated variant of the SOD1 gene, it was seen how they develop ALS disease. If the mutation in the motor neurons was prevented, the mice remained healthy. The surprise appeared with the control group, where only the motoneurons showed the mutation. The theory indicates that in these mice the motoneurons 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 cells close to motor neurons (glia) had some mechanism associated with SOD1 It prevents neurodegeneration.

Specifically, the lifeguards of neurons were astrocytes. If plate-cultured healthy motoneurons joined with SOD1-deficient astrocytes, they died. The conclusion drawn is that the mutated astrocytes release some kind of toxic substance to motor neurons, explaining why only this type of neuron dies in the development of disease. Of course, the toxic agent is still a mystery and the object of investigation.

4. Chronic pain

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

Linda Watkins, a pain researcher at the University of Colorado, suspected that microglia may be involved in chronic pain because it is capable of releasing cytokines, a substance that is secreted in an inflammatory response and that activates the pain.

To see if he was right, he conducted a test on rats with chronic pain caused by damage to the spinal cord. They were administered minocycline, which targets microglia, preventing their activation and, as a consequence, they do not release cytokines. The result was not long in coming, 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, that microglia recognize and defend by secreting cytokines. The problem with chronic pain is that for some reason, the microglia do not stop releasing cytokines, constantly stimulating the production of the sensation of pain, despite the fact that there is no longer any damage.

5. Alzheimer's

Alzheimer's is a disease that destroys neurons and their communication, causing memory loss. A mark 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.

Who generates this toxic accumulation is the 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). The reason for this is still not clear.

Another mark is that around the plates large amounts of microglia are observed, which in an attempt to defend the tissue, group together 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, since it is toxic for them. Also, they have no effect on senile plaque.