Oligodendrocytes

Myelination

Each axon in the human body achieves myelination through a series of consecutive myelin sheaths separated by thin gaps known as the nodes of Ranvier. Each myelin sheath consists of multiple layers of the oligodendrocyte’s cytoplasmic membrane, which wraps around the axolemma, or axonal cell membrane. In the CNS, oligodendrocytes are responsible for creating these myelin sheaths, while Schwann cells perform the same role in the peripheral nervous system (PNS).
To form a myelin sheath, an oligodendrocyte extends a cellular process toward an unmyelinated axon, which wraps around it, making contact with the axolemma and forming a loop known as the inner mesaxon. This wrapping continues in successive loops until multiple layers surround the axon. As this occurs, the cytoplasm within the process is gradually squeezed back toward the glial cell body, leading to the thinning and tightening of the layers around the axon. The resulting layers are tightly compressed, producing structures known as the major dense lines and intraperiod lines, visible under electron microscopy.
The stability of this sheath structure is reinforced by tight junctions—termed autotypic junctions when between glial layers and heterotypic junctions between the glial membrane and the axolemma. Additionally, transmembrane proteins, such as proteolipid protein in the CNS, provide further resilience and integrity to the sheath, ensuring effective insulation and signal transmission along the axon.

Differences between CNS and PNS myelination

While the basic principle of forming a myelin sheath remains similar in the central and peripheral nervous systems, notable distinctions exist between the roles and mechanisms of oligodendrocytes in the CNS and Schwann cells in the PNS. In the CNS, each oligodendrocyte extends multiple processes, enabling it to support up to 50 separate myelin sheaths, which may encase the same or various axons. Consequently, the oligodendrocyte cell body and nucleus remain distant from the sheaths it forms. In contrast, each Schwann cell in the PNS creates only a single myelin sheath, staying closely associated with it by attaching its cell body and nucleus directly to the axolemma, eliminating the need for extended processes.
Structural and nutritional support also differ significantly. In the PNS, connective tissue and a basal lamina provide necessary support to the myelin sheaths. However, in the CNS, support relies on the stable chemical environment maintained by astrocytes, which regulate ion and molecular concentrations in the extracellular fluid. Astrocytes also extend their specialized end-foot processes to the nodes of Ranvier, where they influence ion balance and support the highly concentrated ion channels essential for neural conduction.

The significance of oligodendroglia in the CNS

The fact that most of the neuronal pathways in the human brain and spinal cord comprise myelinated axons is the reason our body is able to respond in time to new stimuli. When assessing the effects of myelination in the CNS due to the presence of the oligodendroglia, two main benefits arise for signal transmission

• Insulation. Myelin consists mainly of lipids (galactocerebroside, sphingomyelin and cholesterol), connected to special proteins that stabilize its form. This unique composition along with the increased thickness of the multiple-layer sheaths insulates the axon from the extracellular space. Consequently, the leakage of ions is significantly limited compared to unmyelinated axons. This insulation provides the basis for greater precision in signaling, with less energy needed, allowing for more complex neuronal circuits.
• Increased conduction speed. The consecution of myelin sheaths (called internodes) separated by the nodes of Ravier forms an axon wrap with alternating insulated and uninsulated regions. This arrangement leads to a phenomenon called “saltatory conduction”. When an action potential is initiated in an unmyelinated axon, it triggers nearby voltage gated channels that in turn activate to propagate the action potential along the axon. It is clear that in an unmyelinated axon the process of action potential propagation includes every part of the axon. On the other hand, the action potential in myelinated axons is propagated only between the nodes of Ravier, “jumping” from node to node and “skipping” the myelinated regions. This is made possible due to the increased concentration of voltage-gated channels at the nodes as well as the insulation of myelin that ensures the continuation of the intracellular ion current. This saltatory conduction of the myelinated axons results in significantly greater speed of signal transmission compared to unmyelinated axons and has made the survival of large multicellular organisms possible, laying the foundation for superior brain functions.
• Nutrition and support. Oligodendrocytes, through myelin, provide to the axons nutrients, regulate ions and molecular levels, and enhance cytoskeletal function, strengthening the axon’s structural integrity.

Myelination-irrelevant functions

A percentage of oligodendrocytes does not show active myelinating activity, though being completely differentiated. These cells are classified as satellite oligodendrocytes and they are not attached via myelin to axons. They are located in the gray matter and their properties are related to the regulation of nervous tissue microenvironment and the replacement of other dysfunctional oligodendrocytes.
Furthermore, oligodendroglia generally plays a major role in neuronal metabolism regulation, expressing growth factors like glial cell line-derived neurotrophic factor (GDNF), or brain-derived neurotrophic factor (BDNF), thus upregulating neuronal growth when needed. Other functions of the oligodendroglia related to damage control and neuronal plasticity are a subject of ongoing studies and are yet to be completely defined.