The microglia or microglial cells are a type of neuroglia of nervous tissue with phagocytic function and that represent one of the most important lines of defense of the central nervous system.
Infectious and pathogenic agents usually do not 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 pathogens reach the brain or spinal cord, the microglial cells must act quickly to phagocytose the foreign bodies before they damage sensitive nerve tissue.
in addition to immunological action, microglia are involved in angiogenesis in the nervous system (blood vessel formation) 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 as they are formed from monocytic precursors, but they are not formed in bone marrow hematopoiesis, but are formed in the yolk sac during a very specific period of embryonic development. Once formed, 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 have already been observed before, the name of microglia was given by Pío del Río Hortega in 1920, so they are also known as Hortega cells.
Morphology and types of microglia
Microglial cells are scattered throughout the Central Nervous System, both in the brain and spinal cord. They are usually 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 common leukocyte antigen. They also feature the Class I/II Major Histocompatibility Complex.
Microglia are cells with high plasticity and can undergo remarkable structural changes depending on their exact location in the Central Nervous System and the specific needs of the organism.
Non-active microglial 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 are activated and change their morphology in different ways.
This form of microglial cells is common in several areas throughout the central nervous system, both in the brain and spinal cord, when foreign bodies are absent.
They are very abundant in the brain parenchyma and constitute between 10 and 20% of glial cells in an adult. They constitute a population of resident cells in nervous tissue that is maintained by local cell division, although previously microglial repopulation was also thought to occur through the uptake of circulating monocytes.
In this form, cells exhibit typical microglial morphology with a small cell body that remains relatively immobile and projections in continuous motion to probe the surrounding area. These projections are called microglial processes.
these cells do not carry out phagocytic activity and are often considered resting or non-active forms, although in reality they are highly active in the 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 an 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, and may represent a population of multipotent cells in the central nervous system of adults and play an important role in its repair.
The reactive form of microglia (historically the term activated microglia has also been used) forms of branched microglia in response to an 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 “brain macrophages” and are related to neuroinflammation. They accumulate in areas where there is an injury and represent the microglia’s form of maximal immune response.
The amoeboid shape of microglia allows free movement of the cell through nervous tissue. It has the ability to phagocytize cellular debris and debris and is associated with central nervous system development in the embryonic, fetal and perinatal stages, when there are numerous cellular debris to be removed.
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 branched microglia found in adults.
Gitter cells are microglial cells resulting from phagocytosis of cellular 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 cells rather than their function or shape, although these microglial populations also have their own functions.
Perivascular microglia are found primarily in the basal lamina of the vascular epithelium of blood vessels that supply the Central Nervous System, and have been shown to play a key role in vascular repair within the nervous system.
Perivascular microglia are constantly repopulated from monocytic bone marrow precursors and respond strongly to macrophage differentiation antigens, hence they are also known as perivascular macrophages.
In turn, the juxtavascular microglia cells are in direct contact with the basal lamina of blood vessels, but outside it.
Both juxtavascular and perivascular microglia express the Major Histocompatibility Complex class II, even at low levels of cytokines. But juxtavascular, unlike perivascular, is not renewed from bone marrow precursors, but by local division like the rest of CNS resident microglia.
Microglial cells perform several 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 beyond that, 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 performed as maintenance of nervous tissue, but also during brain development, regulating the number of neuronal precursor cells and eliminating apoptotic neurons.
It also appears that microglial cells can engage and remove synapses so that they would play an active role in the development of neuronal circuits as well as synaptic pruning.
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 promote an 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.
Activation of microglia causes them to begin expressing histocompatibility complexes on the cell membrane and thus become antigen-presenting cells. Thanks to chemical mediators released by microglia, T lymphocytes migrate to the central nervous system, crossing the blood-brain barrier and joining microglia to recognize antigens and activate other specific immune responses.
After the inflammatory response, the function of microglia is to promote the repair of injured nerve tissue, including the destruction of injured synapses, secretion of anti-inflammatory cytokines, and the attraction of neurons and astrocytes to the injured 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.
For a long time it was thought that microglial cells were formed by hematopoietic stem cell differentiation in the bone marrow, specifically in the myeloid lineage of monocytes, and that they were constantly renewed by the arrival of new monocytic precursors through the circulation.
However, central nervous system resident microglia are formed during embryonic development and subsequently renew themselves without the need for new peripheral monocytic precursors. Only perivascular microglia are renewed from peripheral precursors.
Of 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, mainly myeloid dendritic cells and macrophages, all of which 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.
Microglia constitute the important group of immune cells in the 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 brought under control to promote repair of the damaged area.
The balance between the protective role and the cytotoxic role, which also affects neurons, is fundamental 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 harmful role in neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or Multiple Sclerosis.