- Process of Myelination
- Clinical Conditions
All the organs found in multicellular organisms are made up of two types of cells; parenchymal cells and the supporting cells. The parenchymal cells are involved in performing the main function of that organ such as nephrons in kidneys and myocytes in the heart, etc. The supporting cells are responsible for maintaining the structure of the organ. In addition, they also provide nutrition support and protection to the parenchymal cells. The parenchymal cells cannot perform their function without these supporting cells.
The nervous system is also made up of these two types of cells. The parenchymal cells, in this case, are the neurons that can transmit nerve impulses and can also analyze them. The supporting cells are the glial cells. They are specialized cells abundantly present in both the central as well as the peripheral nervous system. These glial cells provide support in several ways and are necessary for the normal functioning of the nervous system.
Oligodendrocytes are one of these glial cells. They are exclusive to the central nervous system. Their main function is to form the myelin sheath around the axons in the central nervous system. In this article, we will study the structure of oligodendrocytes, their development, functions, classifications, and clinical conditions associated with them. So, keep reading.
Oligodendrocytes are the glial cells having a cell body and cellular processes. As evident from the name, oligodendrocytes (oligo=a few) have a small number of processes coming out of the cell body.
These cells have a small cell body that contains a spherical nucleus. Other organelles are sparse in these cells. The entire cell body is occupied by the spherical nucleus. However, abundant smooth endoplasmic reticulum is present in these cells for myelin synthesis.
Small processes radiate from the cell body of oligodendrocytes. These processes wrap around the axons of the neurons found in the CNS. It will be explained further under the heading of functions.
Oligodendrocytes and the associated processes are not much visible under the light microscope. They appear as small cells with a condensed nucleus and unstained cytoplasm under the light microscope using routine stains. The detailed picture of these cells is obtained using an electron microscope.
Oligodendrocytes present in the central nervous system are divided into two major types; myelinating and non-myelinating.
These are found in the white matter of the brain and spinal cord. These are the primary glial cells in the CNS that are involved in the synthesis of myelin around the nerve fibers.
The cells included in this category can be further classified based on the pattern of myelin sheath formed by them.
- Type I: These cells make several segments of myelin on the same or different axons. The myelin segments thus formed have a diverse orientation.
- Type II: These cells have a structure similar to the type I cells. However, the myelin segments formed by type II cells are arranged parallel to each other.
- Type III: These cells small number of myelin segments on axons having a large diameter.
These are found in the grey matter of the CNS. These cells do not make myelin sheath around the axons. They are also satellite oligodendrocytes. Their function is to regulate the extracellular fluid surrounding the neurons in the grey matter.
The glial cells present in the nervous system are divided into two categories; microglia and macroglia. Both these categories have different embryologic origin. The microglial cells are derived from the mesenchymal cells while the macroglia including oligodendrocytes are derived from neuroectoderm.
Like other macroglial cells, oligodendrocytes are also derived from the neuroepithelium of the neural tube. These neuroepithelial cells differentiate to form glioblasts also called spongioblasts.
These blast cells give rise to oligodendroblasts that are the immediate precursors of oligodendrocytes.
It hs been found that the brain and spinal cord contain different classes of oligodendrocytes. These classes differ with respect to their embryologic development.
In the spinal cord, the neuroepithelial cells first give rise to the motor neurons in the ventral ventricular zone. After this, they switch to form glioblasts. The oligodendroblasts (oligodendrocyte precursor cells) that originate from these glioblasts move throughout the spinal cord and differentiate to form oligodendrocytes.
In case of the brain, oligodendrocyte precursor cells first arise in the forebrain. The first wave of precursor cells arises from the medial eminence. These cells populate the entire embryonic forebrain. These cells are later joined by a second wave coming from the caudal eminence. The third and the final wave of precursor cells arise after birth in the postnatal cortex. All these precursor cells eventually differentiate to from oligodendrocytes.
Differentiation of Precursor cells to Oligodendrocytes
The process of differentiation of oligodendrocyte precursor cells to form oligodendrocytes is regulated via various signaling mechanisms during embryologic development.
The process of myelination also begins during the differentiation process. It has been found that oligodendrocytes can ensheath the axons and form the myelin sheath during the early phase of differentiation. These cells only have a small time span to form the myelin sheath. Once the oligodendrocytes are mature, they cannot ensheath further axons and the myelination process cannot continue.
A detailed account of myelination by the oligodendrocytes is given in the next section.
The most important function of oligodendrocytes is to form the myelin sheath around the axons in the brain and spinal cord. Here, we will discuss details of the myelination process by oligodendrocytes.
Process of Myelination
The process of myelination by oligodendrocytes involves the following steps.
Wrapping of the Axons
The myelination process begins when the processes of oligodendrocytes wrap around the axons found in the white matter. The oligodendrocytes do not wrap randomly around the axons. Rather, the process is regulated by various signaling mechanisms.
The oligodendrocytes select axons having a diameter greater than 0.2 micrometers. One oligodendrocyte can wrap around multiple axons coming from different neurons. The wrapping of multiple axons is a highly coordinated process. The different axons are not wrapped sequentially at different times. Rather, the wrapping of multiple axons takes place simultaneously within a short period of time.
Formation of Multiple Membrane Layers
Recall that the myelin sheath consists of multiple layers of the plasma membrane. Once the oligodendrocyte process has wrapped an axon, it starts rotating around the nerve fiber.
In this way, the axonal nerve fiber gets surrounded by consecutive layers of plasma membrane separated by the cytoplasm. These layers of plasma membrane are rich in phospholipids and myelin proteins that form the biochemical composition of the myelin sheath.
Condensation of Cytoplasm
Initially, the consecutive membrane layers in the myelin sheath are separated by the cytoplasm. This structure appears as a thick indentation on the nerve fiber.
Once the multiple layers are wrapped around the axon, the cytoplasm between these layers starts to condense. The condensation of cytoplasm causes the layers to fuse.
After the condensation of the cytoplasm, the process of myelin sheath formation is complete. It consists of whorls of plasma membrane rich in phospholipids and certain proteins.
Regulation of Myelination Process
Myelination by oligodendrocytes does not occur randomly. Rather, the process takes place in a highly regulated and coordinated fashion.
The onset of myelination is coupled with the differentiation of oligodendrocytes and neurons in the CNS. The onset of myelination in the CNS is determined not only by the differentiation of oligodendrocytes but also by the overall neuronal differentiation.
The neuronal activity in the CNS provides an important signal for the onset of myelination. This was proved by an experiment on rats. The optic nerve of rats who were grown in the dark developed fewer myelinated axons as compared to the optic nerve of normal rats in the control group.
It was found that the degree of myelination is dependant on the neuronal activity. Increasing neuronal activity increases the degree of myelination and vice versa.
Metabolic Support and Nutrition
Recall that we have two types of oligodendrocytes in the CNS. The myelinating oligodendrocytes make the myelin sheath around the axons. On the other hand, the non-myelinating oligodendrocytes provide metabolic support to the neurons.
The satellite or non-myelinating axons are present closely adherent to the neurons in the grey matter. Here, they provide support for the production of some signaling molecules. The oligodendrocytes may provide metabolites for the synthesis of signaling molecules including the following;
- Glial cell line-derived neurotrophic factor (GDNF)
- Brain-derived neurotrophic factor (BDNF)
- Insulin-like growth factor-1 (IGF-1)
The satellite oligodendrocytes are also involved in regulating the extracellular fluid, surrounding the neurons. They can also provide myelin sheath to the damaged cells after a demyelination injury. This function plays a major role in the recovery of the neurons after several injuries to the CNS.
Let us now talk about some pathologies associated with the oligodendrocytes. Different clinical conditions that can affect the functions of oligodendrocytes are discussed below.
Multiple sclerosis is a disorder of nervous system characterized by demyelination of nerve fibers. In this disease, the oligodendrocytes are damaged, resulting in demyelination of nerve fibers in the CNS.
The disease is of unknown origin and can occur due to multiple genetic and environmental factors. The patients present with a wide range of neurological symptoms. These include loss of vision, slurred speech, ataxia, numbness, tingling, muscle spasms, etc. However, the specific symptoms depend on the location of the lesion.
This disorder is characterized by the destruction of white matter in the central nervous system. It is due to the abnormal or imperfect synthesis of the myelin sheath around the axons.
Different pathological variants of this disease are seen. They are caused by different pathologies arising in the oligodendrocytes. For example;
- In one case, oligodendrocytes are destroyed by the accumulation of sulfatides in the cells.
- In another incident, oligodendrocytes are eaten up by the macrophages found in the CNS.
The death of oligodendrocytes due to these reasons results in their inability to form a myelin sheath around the axons. As a result, white matter in the CNS is destroyed.
Oligodendrocytes are susceptible to hypoxic injury when they are in an immature stage. This is commonly seen in the middle period of gestation. The death of immature oligodendrocytes due to hypoxic injury can have harmful consequences on the development of the nervous system.
It impairs the normal growth of neurons and can cause congenital defects. It can result in cerebral palsy.
Some other disorders that can cause the disturbed function of oligodendrocytes include schizophrenia and bipolar disorders.
Moreover, these cells are also susceptible to infection by some viruses like human polyomavirus 2.
- Oligodendrocytes are supportive cells present in the central nervous system.
- These cells consist of a small body with radiating cellular processes. A small spherical nucleus is present in the cell body that also contains a small amount of cytoplasm.
- Oligodendrocytes are divided into two categories:
- Myelinating oligodendrocytes found in the white matter
- Non-myelinating or satellite oligodendrocytes found in the grey matter
- They are derived from the neuroepithelial cells found in the neural tube of an embryo. These cells differentiate into glial cells that make the oligodendrocyte precursor cells. These cells then mature into oligodendrocytes in the brain and spinal cord.
- The process of myelination begins during the differentiation of oligodendroblasts into oligodendrocytes. Mature oligodendrocytes cannot make myelin around the axons.
- The primary function of oligodendrocytes is to make myelin sheath around the axons in the white matter of CNS. They do this by wrapping around the axons and forming layers of the membrane around them. The cytoplasm condenses and the membrane layers fuse to form the myelin sheath.
- One oligodendrocyte can make myelin sheath around several axons.
- Myelination is a highly regulated process. It is directly associated with the neuronal activity in the CNS.
- Satellite oligodendrocytes provide metabolic support to the neurons in the grey matter. They regulate the extracellular fluid and provide metabolites to the neurons for the synthesis of some regulatory molecules.
- Oligodendrocytes are damaged in several clinical conditions. These include multiple sclerosis, leukodystrophies, schizophrenia, bipolar disorders, etc. They are susceptible to hypoxic injury in the early stages of maturation.
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