Oligodendrocytes and the control of myelination in vivo: new insights from the rat anterior medullary velum

Abstract

The rat anterior medullary velum (AMV) is representative of the brain and spinal cord, overall, and provides an almost two-dimensional preparation for investigating axon-glial interactions in vivo. Here, we review some of our findings on axon-oligodendrocyte unit relations in our adult, development, and injury paradigms: (1) adult oligodendrocytes are phenotypically heterogeneous, conforming to Del Rio Hortega's types I-IV, whereby differences in oligodendrocyte morphology, metabolism, myelin sheath radial and longitudinal dimensions, and biochemistry correlate with the diameters of axons in the unit; (2) oligodendrocytes derive from a common premyelinating oligodendrocyte phenotype, and divergence of types I-IV is related to the age they emerge and the presumptive diameter of axons in the unit; (3) during myelination, axon-oligodendrocyte units progress through a sequence of maturation phases, related to axon contact, ensheathment, establishment of internodal myelin sheaths, and finally the radial growth and compaction of the myelin sheath; (4) we provide direct in vivo evidence that platelet-derived growth factor-AA (PDGF-AA), fibroblast growth factor (FGF-2), and insulin-like growth factor-I (IGF-I) differentially regulate these events, by injecting the growth factors into the cerebrospinal fluid of neonatal rat pups; (5) in lesioned adult AMV, transected central nervous system (CNS) axons regenerate through the putatively inhibitory environment of the glial scar, but remyelination by oligodendrocytes is incomplete, indicating that axon-oligodendrocyte interactions are defective; and (6) in the adult AMV, cells expressing the NG2 chondroitin sulphate have a presumptive adult oligodendrocyte progenitor antigenic phenotype, but are highly complex cells and send processes to contact axolemma at nodes of Ranvier, suggesting they subserve a specific perinodal function. Thus, axons and oligodendrocyte lineage cells form interdependent functional units, but oligodendrocyte numbers, differentiation, phenotype divergence, and myelinogenesis are governed by axons in the units, mediated by growth factors and contact-dependent signals.

Proteolipid Promoter Activity Distinguishes Two Populations of NG2-Positive Cells throughout Neonatal Cortical Development

“…We hypothesize that only the PLPexpressing population may become myelinating oligodendrocytes. The other population may differentiate to become the NG2-positive cells found in adult brain, which have been proposed to function in an independent neuromodulatory role in the CNS (Bergles et al, 2000), because they contact nodes of Ranvier (Butt and Berry, 2000) and receive synaptic signals from axons (Bergles et al, 2000).…”

“…On the other hand, other important functions for these adult NG2-positive cells have been proposed that are quite distinct from a role as oligodendrocyte progenitors. Adult NG2-positive cells display a different morphology relative to their younger counterparts (Nishiyama et al, 1999), extending processes along axons to form discrete contacts with axolemma at nodes of Ranvier, perhaps suggesting a role for these cells relating to nodal function (Butt and Berry, 2000). It has also been proposed that adult NG2-positive cells may regulate synaptic growth and plasticity by glutamate signaling at the synapse (Bergles et al, 2000) or that they represent a population of Intensity of fluorescence increased as the cells became obviously myelinating cells, although cell density did not increase.…”

“…4 A, P10). The wave of myelination observed here and in other studies has been proposed to result from local maturation of axons (Hardy and Reynolds,1993;Butt and Berry, 2000), electrical activity (Demerens et al, 1996), or axonal size (Colello et al, 1995). Regardless of the mechanism, if axonal maturation is involved in this signaling, it must be regulated by axonal structure-function at the local level, because there are both ascending and descending axons throughout the cortex, all of which are developing through this period.…”

Ermin, A Myelinating Oligodendrocyte-Specific Protein That Regulates Cell Morphology

“…During development, oligodendrocytes first send multiple filopodia that contact and ensheath axons (Butt and Berry, 2000). After this initial loose ensheathment, non-ensheathing processes are removed and spiral wrapping of the axon commences, eventually forming the compact myelin.…”

Myelination of Motor Neurons Derived from Mouse Embryonic Stem Cells by Oligodendrocytes Derived from Mouse Embryonic Stem Cells in a Microfluidic Compartmentalized Platform

“…In order to avoid these potential problems, some researchers directly transplanted OPCs into the injury site instead of ESCs and observed enhanced remyelination and recovery of motor function [22]. Since studies have reported that astroglial scar is correlated with the failure of remyelination [23,24], it suggested transplantation of OPCs at the early post-injury period after SCI. However, at the acute phase of injury, macrophages infiltrating from the blood and constitutive microglia are activated and may be toxic to the OPCs.…”