Glia 4 lecture

Oligodendrocytes and Myelination

Overview of Oligodendrocytes

• Oligodendrocytes are cells in the central nervous system (CNS) responsible for the process of myelination.

• They myelinate multiple axons, with an average of approximately ten axons per oligodendrocyte.

• They have the ability to sense the health and status of the axons they myelinate.

Schwann Cells

• Schwann cells are found in the peripheral nervous system (PNS) and myelinate axons at a 1:1 ratio (one Schwann cell for each axon).

• Myelination correlates with axonal diameter; larger axons typically have thicker myelin sheaths.

• Schwann cells play a crucial role in supporting and nourishing axons, and they also differentiate into types involved in neuromuscular junctions.

Importance of Myelination

• Myelin is a multi-layered insulating sheath that enhances the speed of electrical conduction along axons.

• Nodes of Ranvier are gaps in the myelin sheath where action potentials are propagated.

• The g-ratio, which describes the number of myelin layers, is consistently about ten layers per axon across both CNS and PNS.

Communication Between Myelin and Axons

• There is interdependence between myelin-producing cells (oligodendrocytes and Schwann cells) and the axons they myelinate.

• Loss of axons leads to degeneration of oligodendrocytes; damaged axons cannot be remyelinated.

Olfactory Bulb Sheathing Cells (OBCs)

• OBCs exist at the interface between the PNS and CNS, specifically in the olfactory bulb, guiding axons towards the olfactory epithelium.

• They exhibit phagocytic abilities and can remove axonal debris, playing a role similar to microglia in the system.

• OBCs secrete neurotrophic factors and possess markers indicative of their function and developmental lineage.

Myelination Process

• Myelination occurs through a developmental process tied to the growth of axons; oligodendrocytes respond to signals from mature axons.

• Initial contact between oligodendrocytes and axons leads to oligodendrocyte differentiation and expression of myelination proteins.

• The structural organization of myelin includes multiple layers and specific molecular patterns that maintain functional compartments like the nodes of Ranvier.

Composition of Myelin

• Myelin consists of approximately 70% lipids (mainly cholesterol, phospholipids, and glycolipids) and 30% proteins.

• Key myelin proteins include myelin binding protein, PLP, P0, and MAG, which facilitate the fusing of myelin layers and retention of axons.

Implications in Disease: Multiple Sclerosis

• Multiple sclerosis (MS) involves autoimmune responses attacking myelin, primarily in white matter areas like the spinal cord and cerebellum.

• The disease goes through relapses and remissions characterized by demyelination and attempts at remyelination.

• The blood-brain barrier breakdown allows autoreactive T-cells and antibodies to enter the CNS, perpetuating inflammatory cycles.

• Chronic phases engage microglia and promote further damage, leading to axonal degeneration, while some neuroprotective activity occurs from oligodendrocyte precursor cells attempting to remyelinate damaged axons.

Summary of Disease Mechanism

• Initiation involves T-cell driven inflammation causing myelin degradation, leading to axonal vulnerability; this creates a cycle of immune reactivation exacerbated by debris in the CNS.

• MRI scans can show active versus chronic lesions in MS patients, reflecting the dynamic nature of myelin integrity during the disease progression.

Conclusion

• Key concepts covered include the functions of oligodendrocytes and Schwann cells, the importance of myelin in neuronal signaling, and the impact of demyelinating diseases on these processes.