Since the belief that glial cells exist only to provide structural support to neuronsIt is more and more common to discover that these microscopic elements are very much involved in the proper functioning of the nervous system. Some of the usual functions of those performed by the glia include defense against damage and invaders, nourishing neurons or enhancing electrical impulse, which makes them much more than just a support. in the development of neurons. as we thought in the past.
From the growing study on glia, we’re also looking to see how these cells (which make up most of the brain components) are involved in diseases and disorders of neurological origin, Which until now was only done in research of different types of neurons.
It is important to understand how involved the neuroglia is in these processes, as this could be one of the ways to find care in the future.
Quick review: what is glia?
In the central nervous system (CNS) we find three main classes of glial cells: Oligodendrocytes, responsible for the placement of the myelin sheath in neurons; microglia, the function is the protection of the brain; and astrocytes, which have a multitude of functions to help neurons.
Unlike the CNS, in the peripheral nervous system (PNS) only one main type of neuroglia is found, the Sch cellsWhen, Which in turn are subdivided into three. Primarily, they are responsible for the generation of the myelin layer in the axons of neurons.
- To learn more about this topic, you can read this article: “Glial cells: much more than the tail of neurons”
Diseases and disorders associated with glia
Currently, there is growing evidence that the neuroglia have a role to play in diseases affecting the CNS, For good and bad. I present here a small list of them, covering different types of diseases, where I discuss the involvement (known today) of glial cells in them. It is likely that many more details will be discovered in the future.
1. Temporary and permanent paralysis
Paralysis is suffered when the connection between a series of neurons is lost, Because his “line of communication” was interrupted. Basically, the glia can release substances called neurotrophs that promote neuronal growth. As in the SNP, this makes it possible to regain mobility over time. But this is not the case in the CNS, suffering from permanent paralysis.
To show that glia is involved in non-recovery, because it is the only one that differentiates this neurological disorder when it occurs in the PNS or the CNS, Albert J. Aguayo, carried out in the 80s an experiment in which rats with damaged (i.e. paralyzed) spinal cord received a sciatic nerve tissue transplant towards the affected area. The result is that in two months the rats again moved with complete naturalness.
In further research, it was found that there is a sum of factors that does not allow a complete recovery of the connection. One of them is the myelin that they produce themselves oligodendrocytes, which by forming the sheath, prevent the growth of the neuron. The purpose of this process is unknown at this time. Another factor is the excess damage caused by the microglia, as the substances it releases to defend the system are also harmful to 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 that of spongiform encephalopathy, because the brains of those affected are full of holes., Giving the sensation of a sponge. One of its variations caused a health scare in the 1990s, known as mad cow disease.
Transmitted if ingested, the prion has the ability to cross the selective blood-brain barrier and become lodged in the brain. In the CNS, it infects both neurons and astrocytes and microglia, replicating and killing cells and creating more and more prions.
I did not forget about the oligodendrocytes, and it seems this type of glia is resistant to infection by prions, but is not resistant to oxidative damage which appear to be part of the struggle of microglia to try to defend neurons. In 2005, the normal state protein generated by the prion was reported to be found in the myelin of the CNS, although it is not known what function it performs there.
3. Amyotrophic lateral sclerosis (ALS)
ALS is a degenerative disease that affects motor neurons, Which gradually lose functionality, resulting in loss of mobility to paralysis.
The cause is a mutation in the gene encoding the enzyme superoxide dismutase 1 (SOD1), which carries a key function for cell survival, which is the removal of free radicals from oxygen. The danger of radicals is that they imbalance the load in the cytoplasm, leading to cell dysfunction and death.
In an experiment with mice with a mutated variant of the SOD1 gene, we saw how they developed ALS. If the motor neuron mutation was prevented, the mice remained healthy. The surprise appeared 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 cause disease. But it didn’t, and to everyone’s surprise, the mice looked healthy. The main thing is that cells close to motor neurons (glia) had a mechanism associated with SOD1 which prevents neurodegeneration.
More precisely, the lifeguards of the neurons were the astrocytes. If healthy plaque-grown motor neurons bind to SOD1-deficient astrocytes, you are dying. The conclusion is that the mutated astrocytes release some kind of substance toxic to the motor neurons, explaining why only these types of neurons die in the development of the disease. Of course, the toxic agent remains a mystery and an object of investigation.
4. Chronic pain
Chronic pain is a disorder in which you the pain cells remain active, without any damage causing their stimulation. Chronic pain develops when there has been a change in the CNS disease circuit after injury or illness.
Linda Watkins, a pain researcher at the University of Colorado, suspects that microglia may be involved in chronic pain so that it can release cytokines, a substance secreted in an inflammatory response and activates pain.
To check if he was right, he performed a test on rats with chronic pain from spinal cord injury. These were given minocycline, which targets microglia, preventing their activation and, therefore, do not release cytokines. The result was not long in coming and the rats stopped suffering.
The same study group discovered the mechanism by which microglia recognize when an area is damaged. Damaged neurons release a substance known as fractalquin, that the microglia recognize and defend by secreting cytokines. The problem with chronic pain is that for some reason the microglia don’t stop releasing cytokines, constantly stimulating the production of the pain sensation, even though there is no more damage.
Alzheimer’s disease is a disease that it destroys neurons and their communication, causing memory loss. A mark of this disease on the anatomy of the brain is the appearance of plaques senile in different regions of the brain. These plaques are an aggregate of a protein called beta-amyloid, which is toxic to neurons.
It is the astrocytes that generate this toxic accumulation. This type of glia has the ability to generate the beta-amyloid peptide because it can process its precursor, the amyloid precursor protein (APP). The reason for this phenomenon is still not clear.
Another mark is that around the plates a large amount of microglia is observed, which in an attempt to defend the tissue, is grouped to fight against the build-up of beta-amyloids and release toxic substances (such as cytokines, chemokines or reactive oxygen), which instead of helping, promote the death of neurons because they are toxic to them . In addition, they have no effect on senile plaque.