Growth Factor Control of CNS Myelination

Abstract

The molecular signals required for initiating myelination and maintenance of the myelin internode are not known. Several growth factor families have been implicated in promoting oligodendrocyte survival or differentiation and may have consequences on formation of myelin. We developed a reliable assay for detecting ensheathment of neurites by oligodendrocytes in spinal cord explants. This system was used to assay the effect of selected growth factors on myelin internode formation. We examined the influence on myelination of the polypeptide growth factors neuregulin (NRG), platelet-derived growth factor (PDGF), leukemia inhibitory factor (LIF), and the thyroid hormone T₃. We found that NRG, PDGF, and T₃ treatments enhanced myelination while LIF treatment inhibited it. We furthermore found that the most potent combination of factors to enhance myelination was NRG and T₃. Our results demonstrate that the role of growth factors on CNS myelination can be reliably studied in a controlled in vitro environment and that the impact of individual or combinations of growth factors on myelination cannot be predicted by their known effects on oligodendrocyte survival, proliferation, or differentiation.

Contrasting effects of mitogenic growth factors on myelination in neuron–oligodendrocyte co‐cultures

“…The level of Nrg-1 type III expressed on the surface of the axon in the PNS has been shown to regulate both whether an axon is myelinated and the thickness of the sheath (Michailov et al, 2004;Taveggia et al, 2005), confirming a central role for Nrg in PNS myelination. Our results, and those of Park et al (2001) using spinal cord explants, show clearly that oligodendrocyte myelination in vitro is enhanced by exogenous Nrg1. Furthermore, our observation that Nrg-blocking antibodies or ErbB4/Fc chimeras can inhibit myelination to a level below that seen in control cultures suggests that endogenous Nrg1 generated in these cultures also contributes to myelination.…”

Effects of Electro-acupuncture on PDGF Expression in Spared Dorsal Root Ganglion and Associated Dorsal Horn Subjected to Partial Dorsal Root Ganglionectomy in Cats

“…PDGF is a major mitogen and stimulant of motility of mesenchymal cells and its isoforms act via two receptor tyrosine kinases, PDGF receptors a and b. Research has shown that PDGF is related to the neuronal trophic activity of the CNS in both embryonic and postnatal phases [25][26][27][28][29]. Also, PDGF might promote functional recovery after spinal cord injury and sciatic nerve injury [30][31][32], indicating its potential role in early neuroplasticity following injury.…”

Neural Stem Cells from Mammalian Brain: Isolation Protocols and Maintenance Conditions

“…Oligodendroglial differentiation can be also enhanced using PDGFa, which promotes their survival (Gogate et al, 1994) in collaboration with NT3 and Triiodothyronine (T3), factors necessary for the correct development of oligodendrocytes and the expression of myelin proteins (Billon et al, 2002;Park et al, 2001). …”