To Be or Not to Be: Environmental Factors that Drive Myelin Formation during Development and after CNS Trauma

Abstract

Oligodendrocytes are specialized glial cells that myelinate central nervous system (CNS) axons. Historically, it was believed that the primary role of myelin was to compactly ensheath axons, providing the insulation necessary for rapid signal conduction. However, mounting evidence demonstrates the dynamic importance of myelin and oligodendrocytes, including providing metabolic support to neurons and regulating axon protein distribution. As such, the development and maintenance of oligodendrocytes and myelin are integral to preserving CNS homeostasis and supporting proper functioning of widespread neural networks. Environmental signals are critical for proper oligodendrocyte lineage cell progression and their capacity to form functional compact myelin; these signals are markedly disturbed by injury to the CNS, which may compromise endogenous myelin repair capabilities. This review outlines some key environmental factors that drive myelin formation during development and compares that to the primary factors that define a CNS injury milieu. We aim to identify developmental factors disrupted after CNS trauma as well as pathogenic factors that negatively impact oligodendrocyte lineage cells, as these are potential therapeutic targets to promote myelin repair after injury or disease.

Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

“…Herein, the following nine postulates from the book chapter "Microglia" by Pio del Rio-Hortega in 1932 still hold true to this very time and will be entered in this section (Table 1) [103,104]. [105,106,107]. OL derived myelin additionally serves as a protective sheath in myelinated axons in order to provide for long-term axon integrity, maintenance and survival as well as increasing the speed of information transmission from neuron to neuron or regional bundles to distant bundles via white matter tracts as in optic nerves and corpus callosum.…”

Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part III: Oligodendrocyte and Myelin

“…The myelin sheath provides axonal protection and allows the saltatory conduction of the action potential. Oligodendrocytes (OLs), oligodendrocyte precursor cells (OPC), and oligodendrocyte lineage cells are specialized glial cells responsible for the synthesis, wrapping ensheathment, and compacting of myelin in myelinated axons [1][2][3]. Rudolf Ludwig Virchow (1821-1902) introduced the term myelin and defined it as medullary matter (Markstoff), or myeline, that in extremely large quantity fills up the interval between the axon axis-cylinder and the sheath in primitive nerve-fibers [4].…”

“…They also may occur in groups or nests and are more often found in the white matter regions of the brain. In addition to their small cytoplasmic volume, they have multiple protoplasmic extensions, which allow OLs to concurrently myelinate multiple axons [1][2][3][4]. Depicts an astrocyte (AC) with electron lucent cytoplasm and a ramified microglial cell (rMGC) with its electron dense cytoplasm.…”

“…These myelin lamella that enwrap multiple unmyelinated axons increase the speed of neuronal transmission of their action potentials via membrane depolarization by high-density voltage-gated sodium channels that creates the saltatory (jumping) conduction of their action potentials and signaling at the nodes of Ranvier ( Figure 1B). Importantly, this saltatory conduction allows electrical nerve signals to be propagated long distances at high rates without any degradation of the action potential signaling [1][2][3][4].…”

Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Obesity, Aging, Intersects and Continuum Of Progression

“…Oligodendrocytes (OLs), oligodendrocyte precursor cells (OPC), and oligodendrocyte lineage cells are specialized glial cells responsible for the synthesis, wrapping ensheathment, and compacting of myelin in myelinated axons [105,106,107]. OL derived myelin additionally serves as a protective sheath in myelinated axons in order to provide for long-term axon integrity, maintenance and survival as well as increasing the speed of information transmission from neuron to neuron.…”