What is microglia or microglial cells?

The microglia or microglial cells are a type of neuroglia of nervous tissue with phagocytic function and that they represent one of the most important lines of defense of the Central Nervous System.

Infectious and pathogenic agents do not usually reach the Central Nervous System due to the blood-brain barrier. This barrier also prevents the passage of most antibodies and antibody immune cells, so if any pathogen reaches the brain or spinal cord, the microglial cells must act quickly to phagocytize the foreign bodies before they damage the sensitive nervous tissue.

Besides the immune actionmicroglia are involved in the angiogenesis within the nervous system (formation of blood vessels) and in the modeling of nerve connections by regulating controlled cell death (apoptosis) and synapse elimination.

Microglia can be considered as a type of leukocyte, since it is formed from monocytic precursors, but they are not formed in the hematopoiesis of the bone marrow, but rather are formed in the yolk sac during a very specific period of embryonic development. After forming, they migrate to the brain mesenchyme and here they are constantly renewed throughout life by themselves without the intervention of new monocytic precursors.

Although they were observed before, the name of microglia was given by Pío del Río Hortega in 1920, hence they are also known as Hortega's cells.

Morphology and types of microglia

Microglial cells are scattered throughout the Central Nervous System, both in the brain and spinal cord. They are generally small cells with little cytoplasm and a variable number of short, irregular cell projections.

In the cytoplasm they contain an oval or roughly triangular nucleus, lysosomes, and residual bodies. As cells derived from the myeloid lineage, microglial cells present the leukocyte common antigen. They also present the Major Histocompatibility Complex class I/II.

Shapes

Microglia are cells with high plasticity and they can undergo notable structural changes depending on the exact location in the Central Nervous System and the specific needs of the organism.

Non-active microglia cells are constantly monitored by the central nervous system and when damage occurs, for example in the presence of a pathogen or dead cell debris, they become activated and change their morphology in different ways.

branched microglia

This form of microglial cells are common in various areas distributed throughout the central nervous system, both in the brain and spinal cord, when no foreign bodies are present.

They are very abundant in the brain parenchyma and constitute between 10 and 20% of the glial cells in an adult. They constitute a resident cell population of nervous tissue that is maintained by local cell divisionalthough previously it was also thought that microglia repopulation occurred by uptake of circulating monocytes.

In this form, the cells present the typical morphology of microglia with a small cell body that remains relatively immobile and continuously moving projections to probe the surrounding area. These projections are called microglial processes.

these cells do not perform phagocytic activity and are often considered the resting or non-active formalthough in reality they present high activity in search and identification of possible attacks and in the maintenance of nervous system homeostasis.

Branched microglia can transform into the reactive form at any time in response to injury or attack. It also seems that they can transform into other cells of the central nervous system, such as astrocytes, oligodendrocytes or even neurons, so they could represent a population of multipotent cells in the central nervous system of adults and play an important role in its repair.

reactive microglia

The reactive form of microglia (historically the term activated microglia has also been used) forms from branching microglia in response to injury or a pathogen. When activated, they proliferate and transform into cells with an elongated shape, without projections and with a large number of cells. lysosomes and phagosomes.

Reactive microglia are also known as the "brain macrophages» and are related to neuroinflammation. They accumulate in areas where there is an injury and represent the form of maximal immune response of microglia.

amoeboid microglia

The amoeboid shape of microglia allows free movement of the cell through the nervous tissue. It has the ability to phagocytize cellular debris and debris and are associated with central nervous system development in the embryonic, fetal and perinatal stage, when there are numerous cellular debris to remove.

In the postnatal stage, they appear to be involved in the histogenesis of central nervous tissue, for example by removing superfluous or inappropriate neuronal axons.

Amoeboid microglia transform into the branching microglia found in adults.

Gitter cells

Gitter cells are microglial cells resulting from the phagocytosis of cell debris or infectious material. They have cytoplasm full of granules and saturated phagocytic capacity.

Perivascular and juxtavascular microglia

Unlike the other types of microglia, perivascular and juxtavascular microglia refer to the location of the cells and not to their function or shape, although these microglial populations also have their own functions.

Perivascular microglia are found primarily enclosed in the basal lamina of vascular epithelium of the blood vessels that irrigate the Central Nervous System, and have shown a fundamental role in vascular repair within the nervous system.

Perivascular microglia are constantly repopulated from monocytic precursors from the bone marrow and respond strongly to macrophage differentiation antigens, so they are also often known as perivascular macrophages.

For their part, the cells of the juxtavascular microglia are in direct contact with the basal lamina of the blood vessels, but outside of it.

Both juxtavascular and perivascular microglia express Major Histocompatibility Complex class II even at low levels of cytokines. But the juxtavascular, unlike the perivascular, is not renewed from bone marrow precursors but by local division like the rest of the resident microglia of the CNS.

Functions

Microglia cells perform various functions within the Central Nervous System that can be classified mainly into two categories: immune response and maintenance of homeostasis.

Phagocytosis and removal of waste products

Microglia are very sensitive to small chemical changes in their environment, but in addition, these cells continually scan their surroundings for objects and physical changes. This function is performed by the amoeboid form and the resting form.

If in this scan of the environment the microglial cell finds a body that it does not recognize, such as external pathogens, a damaged cell, remnants of apoptosis or senile plaques, the cell is activated and phagocytoses the material found.

This function is carried out as maintenance of the nervous tissue, but also during brain development by regulating the number of neuronal precursor cells and eliminating apoptotic neurons.

It also appears that microglial cells can wrap and remove synapsesso they would have an active role in the development of neuronal circuits as well as in synaptic pruning.

cytotoxicity

In addition to phagocytosis, microglial cells secrete cytotoxic substances, such as hydrogen peroxide and nitric acid, which contribute to the destruction and removal of pathogens and damaged self cells.

Extracellular signaling in the immune response

Related to the phagocytic function described above, microglia maintain homeostasis in uninfected areas and regions and promotes inflammatory response in infected areas or with damaged tissue.

To generate the inflammatory response, microglia use a complex system of extracellular signaling molecules with which they communicate with other microglial cells, astrocytes, neurons, T cells, and myeloid precursors.

The activation of microglia causes them to begin to express histocompatibility complexes in the cell membrane and thus to become antigen presenting cells. Thanks to the chemical mediators released by the microglia, the T lymphocytes migrate to the central nervous system, crossing the blood-brain barrier and joining the microglia to recognize the antigens and activate other specific immune responses.

Repair

After the inflammatory response, the function of microglia is aimed at promoting the repair of damaged nerve tissue, including the destruction of damaged synapses, secretion of anti-inflammatory cytokines, and the attraction of neurons and astrocytes to the damaged area.

Without the action of microglia, it is believed that the repair and regeneration of damaged neuronal circuits would be much slower or even impossible in some areas of the central nervous system.

Microgliogenesis

For a long time it was thought that microglial cells were formed by differentiation of the hematopoietic stem cell in the bone marrow, specifically in the myeloid lineage from monocytes, and that they were constantly renewed by the arrival of new monocytic precursors through the circulation. .

However, the resident microglia of the central nervous system is formed during embryonic development and later renews itself without the need for new peripheral monocytic precursors. Only perivascular microglia are renewed from peripheral precursors.

Having a myeloid origin, microglia originate in the mesoderm, unlike the rest of the glial cells that originate in the neuronal tube.

Monocytes also differentiate into other cell types that migrate to various peripheral tissues, primarily myeloid dendritic cells and macrophagesand they all share many functional and biochemical similarities.

For example, microglia and macrophages use phagocytosis and cytotoxicity to destroy potentially harmful foreign bodies, and both act as antigen-presenting cells.

medical implications

Microglia constitute the group of immune cells important nervous system with a function, as mentioned, similar to the function of macrophages in peripheral tissues. In the presence of an injury or pathogens, they become active, change shape and migrate to the damaged area where they eliminate pathogens and damaged cells.

As part of the response, microglia secrete numerous molecular mediators that regulate the immune response, such as cytokines, chemokines, prostaglandins, and cytotoxic agents.

In addition, microglia also produce anti-inflammatory cytokines once the situation has been controlled to promote repair of the damaged area.

The balance between the protective role and the cytotoxic role, which also affects neurons, is key during the development of the nervous system and during its repair, but it can be affected. In this sense, microglia are widely studied for their detrimental role in neurodegenerative diseasesIt's like Alzheimer's, Parkinson's or Multiple Sclerosis.

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