Glial cells: much more than the glue of neurons

It is very common that, when talking about a person's intelligence, we refer specifically to a very specific type of cells: neurons. Thus, it is normal to call mononeuronal to those who attribute low intelligence in a derogatory way. However, the idea that the brain is essentially equivalent to a set of neurons is increasingly out of date.

The human brain contains more than 80 billion neurons, but this only accounts for 15% of the total cells in this set of organs.

The remaining 85% is occupied by another type of microscopic body: the so-called glial cells.. As a whole, these cells form a substance called glia or neuroglia, which extends through all the recesses of the nervous system.

Currently, the glia is one of the fields of study with the greatest progress in neurosciences, looking to reveal all his tasks and interactions that they carry out so that the nervous system works as it does. And it is that the brain currently cannot be understood without understanding the involvement of the glia.

The discovery of glial cells

The term neuroglia was coined in 1856 by the German pathologist Rudolf Virchow. This is a word that in Greek means "neuronal (neuro) glue (glia)", since at the time of its discovery neurons were thought to be linked together to form nerves and, it is more, than the axon it was a collection of cells instead of a part of the neuron. For this reason, it was assumed that these cells that they found near the neurons were there to help structure the nerve and facilitate the union between them, and nothing else. A fairly passive and auxiliary role, in short.

In 1887, the famous researcher Santiago Ramón y Cajal concluded that neurons were independent units and that were separated from the others by a small space that later became known What synaptic space. This served to disprove the idea that axons were more than just parts of independent nerve cells. However, the idea of ​​glial passivity remained. Today, however, its importance is being discovered to be much greater than previously assumed.

In a way, it is ironic that the name that has been given to neuroglia is that. It is true that it does help in the structure, but it not only performs this function, but they are also for your protection, repair of damages, improves nerve impulse, offers energy, and even controls the flow of information, among many more functions discovered. They are a powerful tool for the nervous system.

Glial cell types

Neuroglia is a set of different types of cells that have in common that they are found in the nervous system and are not neurons.

There are quite a few different types of glial cells, but I will focus on talking about the four classes that are considered more important, as well as in explaining the most prominent functions discovered up to today. As I have said, this field of neuroscience advances more every day and surely in the future there will be new details that are unknown today.

1. Schwann cells

The name of this glia cell is in honor of its discoverer, Theodore Schwann, best known as one of the fathers of the Cell Theory. This type of glial cell is the only one found in the Peripheral Nervous System (PNS), that is, in the nerves that run throughout the body.

While studying the anatomy of nerve fibers in animals, Schwann observed some cells that were attached along the axon and gave the feeling of being something like small "Pearls"; Beyond this, he did not give them more importance. In future studies, it was discovered that these microscopic bead-shaped elements were actually myelin sheaths, an important product that generates this type of cell.

Myelin is a lipoprotein that provides insulation against electrical impulse to the axon, that is, it allows the action potential to be held for a longer time and at a greater distance, making the electrical shots go faster and not dispersing through the neuron membrane. That is, they act like the rubber that covers a cable.

Schwann cells they have the ability to secrete various neurotrophic components, including the "Nerve Growth Factor" (NCF), the first growth factor found in the nervous system. This molecule serves to stimulate the growth of neurons during development. In addition, as this type of neuroglia surrounds the axon like a tube, it also has an influence to mark the direction in which it should grow.

Beyond this, it has been seen that when a nerve of the PNS has been damaged, FCN is secreted so that the neuron can grow back and regain its functionality. This explains the process by which the temporary paralysis that muscles suffer after suffering a tear disappears.

The three different Schwann cells

For early anatomists there were no differences in Schwann cells, but with advances in microscopy have been able to differentiate up to three different types, with structures and functions well differentiated. The ones that I have been describing are the "myelinic" ones, since they produce myelin and are the most common.

However, in neurons with short axons, another type of Schwann cell called "unmyelinated" is foundas it does not produce myelin sheaths. These are larger than the previous ones, and inside they house more than one axon at a time. They do not appear to produce myelin sheaths, since with its own membrane it already serves as insulation for these smaller axons.

The last type of this form of neuroglia is found in the synapse between neurons and muscles. They are known as terminal or perisynaptic Schwann cells. (between the synapse). Its current role was revealed in an experiment conducted by Richard Robitaille, a neurobiologist at the University of Montreal. The test consisted of adding a false messenger to these cells to see what happened. The result was that the response expressed by the muscle was altered. In some cases the contraction was increased, in other cases it decreased. The conclusion was that this type of glia regulates the flow of information between the neuron and the muscle.

2. Oligodendrocytes

Within the Central Nervous System (CNS) there are no Schwann cells, but neurons have another form of myelin coating thanks to an alternative type of glial cells. This function is carried out the last of the great types of neuroglia discovered: the one formed by oligodendrocytes.

Their name refers to how the first anatomists who found them described them; a cell with a multitude of small extensions. But the truth is that the name does not accompany them much, since some time later, a pupil of Ramón and Cajal, Pío del Río-Hortega, designed improvements in the stain used at the time, revealing the true morphology: a cell with a couple of long extensions, like arms.

Myelin in the CNS

One difference between oligodendrocytes and myelinated Schwann cells is that the former do not envelop the axon with its body, but they do it with their long extensions, as if they were tentacles of an octopus, and it is through them that myelin is secreted. In addition, the myelin in the CNS is not only there to isolate the neuron.

As Martin Schwab demonstrated in 1988, the deposition of myelin on the axon in cultured neurons hinders their growth. Searching for an explanation, Schwab and his team were able to purify several myelin proteins that cause this inhibition: Nogo, MAG, and OMgp. The funny thing is that it has been seen that in the early stages of brain development, the MAG protein of myelin stimulates the growth of the neuron, doing a reverse function of the neuron in Adults. The reason for this inhibition is a mystery, but scientists hope its role will soon be known.

Another protein found in the 90s is also found in myelin, this time by Stanley B. Prusiner: Prion Protein (PrP). Its function in a normal state is unknown, but in a mutated state it becomes a Prion and generates a variant of Creutzfeldt-Jakob disease, commonly known as cow disease crazy. The prion is a protein that gains autonomy, infecting all the cells of the glia, which generates neurodegeneration.

3. Astrocytes

This type of glial cell was described by Ramón y Cajal. During his observations of neurons, he noticed that there were other cells near the neurons, star shaped; hence its name. It is located in the CNS and the optic nerve, and is possibly one of the glia that carries out a greater number of functions. Its size is two to ten times larger than that of a neuron, and it has very diverse functions

Blood brain barrier

Blood does not flow directly into the CNS. This system is protected by the Blood Brain Barrier (BBB), a highly selective permeable membrane. Astrocytes actively participate in it, being in charge of filtering what can happen to the other side and what not. Mainly, they allow the entry of oxygen and glucose, to be able to feed the neurons.

But what happens if this barrier is damaged? In addition to the problems that are generated by the immune system, groups of astrocytes travel to the damaged area and join each other to form a temporary barrier and stop bleeding.

Astrocytes have the ability to synthesize a fibrous protein known as GFAP, with which they gain robustness, in addition to secreting another followed by proteins that allows them to gain impermeability. In parallel, astrocytes secrete neurotrophs, to stimulate regeneration in the area.

Potassium Battery Recharge

Another of the described functions of astrocytes is their activity to maintain the action potential. When a neuron generates an electrical impulse, it collects sodium ions (Na +) to become more positive with the outside. This process by which the electrical charges outside and inside the neurons are manipulated produces a state known as depolarization, which causes the electrical impulses that travel through the neuron to be born until they end in the synaptic space. During your trip, the cell environment always seeks the balance in the electrical charge, so this time it loses potassium ions (K +), to match the extracellular environment.

If this always happened, in the end a saturation of potassium ions would be generated outside, which would mean that these ions would stop leaving the neuron, and this would result in the inability to generate the electrical impulse. This is where astrocytes come into the picture, who they absorb these ions inside to clean the extracellular space and allow more potassium ions to be secreted. Astrocytes do not have any problem with charge, since they do not communicate by electrical impulses.

4. Microglia

The last of the four major forms of neuroglia is microglia.. This was discovered before oligodendrocytes, but it was thought to come from blood vessels. It occupies between 5 to 20 percent of the glia population of the CNS, and its importance is based on the fact that it is the basis of the brain's immune system. By having the protection of the Blood-brain Barrier, the free passage of cells is not allowed, and this includes those of the immune system. Thus, the brain needs its own defense system, and this is formed by this type of glia.

The CNS immune system

This glia cell is highly mobile, allowing it to react quickly to any problem it encounters in the CNS. The microglia have the ability to devour damaged cells, bacteria and viruses, as well as to release a series of chemical agents with which to fight against invaders. But the use of these elements can cause collateral damage, since it is also toxic to neurons. Therefore, after the confrontation, they have to produce neurotrophic astrocytes to facilitate the regeneration of the affected area.

Earlier, I talked about damage to the BBB, a problem that is generated in part by the side effects of microglia when leukocytes cross the BBB and enter the brain. The interior of the CNS is a new world for these cells, and they react primarily as unknown as if it were a threat, generating an immune response against it. The microglia initiates the defense, causing what we could say a "civil war", which causes a lot of damage to neurons.

Communication between the glia and neurons

As you have seen, the glia cells carry out a wide variety of tasks. But a section that has not been clear is whether neurons and glia communicate with each other. The first researchers already realized that the glia, unlike neurons, do not generate electrical impulses. But this changed when Stephen J. Smith checked how they communicate, both with each other and with neurons.

Smith had the intuition that the neuroglia uses the calcium ion (Ca2 +) to transmit information, since this element is the most used by cells in general. Somehow, he and his companions jumped into the pool with this belief (after all, the "popularity" of an ion doesn't tell us much about its specific functions either), but they got it right.

These researchers designed an experiment that consisted of a culture of astrocytes to which fluorescent calcium was added, which allows their position to be seen through fluorescence microscopy. In addition, he added in the middle a very common neurotransmitter, the glutamate. The result was immediate. For ten minutes they were able to see how the fluorescence entered the astrocytes and traveled between the cells as if it were a wave. With this experiment they showed that the glia communicates with each other and with the neuron, since without the neurotransmitter the wave does not start.

The latest known about glial cells

Through more recent research, the glia have been found to detect all types of neurotransmitters. Furthermore, both astrocytes and microglia have the ability to manufacture and release neurotransmitters (although at these elements are called gliotransmitters because they originate in the glia), thus influencing the synapses of the neurons.

A current field of study is seeing up where glia cells influence overall brain function and complex mental processes, What The learning, the memory or the dream.