How oligodendrocytes insulate brain neurons
Insulating neuron axons
Oligodendrocytes are glial cells in the central nervous system (CNS) responsible for myelination of neurons. Similar to other glial cells, oligodendrocytes possess a cell body (soma) from which many processes extend. Extension and retraction of oligodendrocyte processes are crucial for their migration through the brain and their contact with neuron axons.
The membrane of the processes has a high content of lipid bound protein called lipophilin. Upon contact with neuron axons in the brain, oligodendrocyte exploratory processes convert to flat sheets that spread and wind around neuron axons to create a multilayered or laminar cover. The laminar structure then compacts extruding almost all of its cytoplasm and is referred to as myelin.
Myelination and electrical activity
Myelination of CNS neurons by oligodendrocytes enables rapid propagation of electrical signals (action potentials) along neuronal axons. Myelination increases conduction velocity of neuron axons by at least 50 times.
Besides axonal conduction speed, myelin also protects neuron axons against inflammatory and oxidative injury by placing multiple layers of lipid between axons and highly reactive oxygen-containing molecules. The human brain, and that of other mammals, is characterized by a high rate of production of such reactive molecules. Such insulation is important, because destruction of the myelin sheath around nerve axons rapidly leads to neuron death.
There is evidence that myelination of neurons is partly driven by the level of electrical activity in axons themselves. For example, changes in neuronal activity can increase myelination of neurons in the motor cortex when new learning involves intricate motor skill patterns requiring speed and precision, such as playing musical instruments.
A suggested mechanism for this process is hypothesized to involve axonal release of ATP that stimulates adjacent astrocytes to release the pro-myelination cytokine LIF, which in turn signals to oligodendrocytes to increase the level of myelination.
Time course of neuron myelination
While myelination of neurons in the human brain starts in late fetal life and peaks in infants, certain associative regions continue to increase their myelination into the 5th and 6th decade of life.
White matter (neuron axons and glial cells) of the adult brain is densely populated with both mature oligodendrocytes and oligodendrocyte precursor cells. Regeneration of oligodendrocytes in the CNS after injury depends upon activation of the widespread pool of oligodendrocyte precursor cells.
A large number of cellular factors and extracellular signaling molecules have been implicated in maturation of oligodendrocyte precursor cells. An excellent review of this process by Ben Emery is available at Science, VOL 330, 2010, pages 779-772.
CNS myelin as a disease target
Several disease processes in human include removal of myelin from neurons in the CNS. Among these are Multiple Sclerosis (MS) and Alzheimer’s. MS is an inflammatory disease in which myelin around axons of the brain and spinal cord are damaged and scarred. In MS the myelin destruction becomes progressively widespread throughout the CNS. The precise cause of MS is still unknown but it is thought that the oligodendrocytes die.
In contrast, demyelination of axons in Alzheimer’s, a form of dementia associated with brain inflammation, is a more discrete process. In Alzheimer’s there is a focal loss of oligodendrocytes associated with amyloid beta plaque. Plaque free regions display little to no demyelination or oligodendrocyte loss.
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Margaret Thompson Reece PhD, physiologist, former Senior Scientist and Laboratory Director at academic medical centers in California, New York and Massachusetts and CSO at Serometrix LLC is now CEO at Reece Biomedical Consulting LLC.
Dr. Reece is passionate about helping students, online and in person, pursue careers in life sciences. Her books “Physiology: Custom-Designed Chemistry” (2012), “Inside the Closed World of the Brain” (2015) and the workbook (2017) companion to her online course “30-Day Challenge: Craft Your Plan for Learning Physiology” are written for those new to life science. More about her books can be found at amazon/author/margaretreece.
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